摘要
目的:基质金属蛋白酶(Matrix Metalloproteinases,MMPs)是高度保守的依赖于Zn2+的蛋白水解酶家族,是肿瘤发生、侵袭和转移过程中起关键作用的酶之一。研究表明,多数MMPs在正常组织中表达量很低,而在肿瘤组织中,各种类型MMPs的表达均有不同程度的增高。MMPs不仅参与肿瘤的侵袭和转移过程,也与肿瘤发生发展的许多因素有关,包括细胞的生长、凋亡、血管生成和免疫监视等。MMPs基因启动子区的单核苷酸多态性(Single Nucleotide Polymorphism, SNPs)可能影响其基因的转录水平和蛋白质的表达,从而影响肿瘤等疾病的发生、发展及预后。脑胶质瘤(Glioma)是最常见的原发性脑肿瘤,尽管近年来在影像诊断、神经外科技术、放射治疗、化疗等方面已取得较大进展,该肿瘤的生存率并无明显提高。星形细胞瘤(Astrocytoma)是脑胶质瘤中最常见的病理类型,其病因尚未明确,近年研究提示遗传因素可能在星形细胞瘤的发生中起重要作用。鉴于有报道显示MMPs在星形细胞瘤中的表达增高,我们推测,其启动子区的基因多态性可能通过改变转录活性而影响星形细胞瘤的发生。最近,McCready等的研究显示,多形性胶质母细胞瘤组织中的MMP-1 2G/1G SNP可能在胶质母细胞瘤形成和侵袭中发挥作用,其他MMPs基因多态性与神经胶质细胞瘤的关系国内外尚未见报道。另外,MMPs基因启动子区多态性与肿瘤组织中MMPs蛋白表达及mRNA转录水平的关系尚不清楚。为此,本研究拟通过基于我院手术和病理证实的病例-对照研究,分析MMP-1、MMP-3、MMP-7和MMP-9基因启动子区基因多态性与成人脑星形细胞瘤易感性的关系,同时观察星形细胞瘤中MMP-1、3、7、9的蛋白及mRNA的表达与星形细胞瘤发生、发展的关系,特别是个体对星形细胞瘤的遗传易感性及其发生、发展的分子机制,为星形细胞瘤的预防和治疗提供理论依据。我们分三部分进行了研究。
第一部分MMP-1、3、7、9基因启动子区多态性与成人星形细胞瘤的关联研究
方法
采用基于医院的病例对照方法。收集236例成人脑星形细胞瘤病例的手术标本,经组织学诊断后,以蛋白酶K消化、酚-氯仿抽提法提取肿瘤组织DNA。抽取366例健康对照外周静脉血5ml,以蛋白酶K消化-饱和氯化钠盐析法提取白细胞DNA。MMP-1 -1607 2G/1G, MMP-3 -1171 5A/6A, MMP-7 -181A/G, MMP-9 -1562 C/T基因型检测应用聚合酶链反应-限制性片段长度多态性分析( Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)方法进行。应用卡方检验比较对照组及病例组基因型频率的观察值与预期值,进行Hardy-Weinberg平衡检验。病例组与对照组的性别、基因型和等位基因型分布比较均采用四格表卡方检验。以非条件Logistic回归法计算表示相对风险度的比值比(Odds Ratio,OR)及其95%的可信区间(Confidence Interval,CI),并经性别、年龄校正。
结果
1 MMP-1-1607 2G/1G SNP的等位基因型及基因型总体分布在星形细胞瘤患者组和正常对照组之间有显著性差异(分别为P=0.002和﹤0.001)。与2G/2G基因型相比,1G/1G基因型可显著降低该肿瘤的发病风险,经性别、年龄校正的OR值为0.58(95%CI为0.42～0.79),而2G/1G基因型对该肿瘤的易感性无显著影响(校正OR值为0.74,95%CI为0.51～1.08)。根据性别、发病年龄(≤45岁或>45岁)进行的分层分析显示了相似的结果。根据WHO病理分级进行的分层分析显示,1G/1G基因型均可显著降低II、III级肿瘤的发病风险,而对I、IV级肿瘤的发病风险无显著影响。
2 MMP-3 -1171 6A/5A多态性等位基因型及基因型总体分布在肿瘤组和正常对照组之间无显著性差异(P>0.05)。根据性别、发病年龄(≤45岁或>45岁)、WHO病例分级进行的分层分析显示,肿瘤组和正常对照组之间的基因型分布均无显著性差异。与MMP-3 6A/6A基因型相比,在总体比较及分层分析中均未发现6A/5A或5A/5A基因型可改变星形细胞瘤的发病风险,经性别、年龄校正的OR值分别为1.09(95% CI=0.75～1.57)和0.95 (95% CI=0.54～1.69)。
3 MMP-7 -181 A/G SNP的基因型及等位基因型分布在星形细胞瘤及正常对照组有显著性差异(P=0.001)。与MMP-7 A/A基因型相比,A/G及G/G基因型可显著增加星形细胞瘤的发病风险,经性别、年龄较正的OR值分别为1.69及2.77(95% CI=1.01～2.84及1.27～6.02)。根据发病年龄进行的分层分析显示,与MMP-7 A/A基因型相比,G/G基因型可使45岁以下个体发生星形细胞瘤的风险增加3倍左右(校正OR=3.16,95%CI=1.09～9.16),而对45岁以上个体对此肿瘤的发病风险无显著影响。根据性别的分层分析显示,与MMP-7 A/A基因型相比,携带G/G基因型的男性个体发生星形细胞瘤的风险可增加3倍以上(校正OR=3.24,95%CI=1.12～9.41)。根据WHO病理分级进行的分层分析显示,MMP-7 G/G基因型较A/A基因型携带者发生II～IV级星形细胞瘤的风险增加3倍左右,校正OR值分别为2.95 (95% CI = 1.21～7.17), 3.32 (95% CI = 1.15～9.61),和3.25 (95% CI = 1.10～9.62),且A/G基因型可增加II级星形细胞瘤的发病风险约2倍(校正OR=2.06, 95% CI = 1.05～4.05),而此MMP-7基因多态性对I级星形细胞瘤的发病风险无显著影响。4 MMP-9 -1562 C/T SNP的等位基因型及基因型总体分布在肿瘤组和正常对照组之间无显著性差异(P值分别为0.926和0.818)。与C/C基因型相比,C/T+T/T基因型不能改变星形细胞瘤的发病风险(经性别、年龄校正OR值为1.09,95%CI为0.73～1.64)。根据性别、发病年龄、WHO病理分级进行的分层分析,也未发现C/T+T/T基因型与胶质瘤的发病风险相关。
结论
1总体分析及根据性别、发病年龄、病理分级进行的分层分析均显示,MMP-3 -1171 5A/6A多态性、MMP-9 -1562 C/T多态性不能改变星形细胞瘤的发病风险;
2 MMP-1-1607 2G/1G多态性可影响星形细胞瘤的发病风险。与人群中占分布优势的2G/2G基因型相比,1G/1G基因型可显著降低该肿瘤的发病风险;
3 MMP-7-181A/G多态性对星形细胞瘤发病风险有明显影响。与A/A基因型相比,携带G等位基因型(A/G和G/G基因型)可显著增加个体对星形细胞瘤的发病风险,此现象在45岁以下人群、男性个体中尤为明显。
第二部分MMP-1、3、7、9蛋白表达与成人星形细胞瘤临床病理分级的关系
方法
收集上述星形细胞瘤标本中70例及8例脑外伤病人行手术内减压的脑组织石蜡包埋手术标本。光镜下常规病理形态学观察,确定星形细胞瘤的病理诊断及病理分级(WHO 1999)。组织标本MMP-1、3、7和9的蛋白表达以免疫组织化学方法检测,采用即用型S-P试剂盒进行。各组数据之间的相关性,采用Kendall’s tau-b等级相关分析,相关系数用tb值表示,P<0.05为显著性检验水准。不同组间蛋白表达阳性率比较用X2检验。
结果
1非肿瘤脑组织、I～IV级星形细胞瘤组织中MMP-1蛋白的阳性表达率分别为12.5%、75%、86%、90%、100%,各组间MMP-1蛋白的表达有显著性差异(X2=28.204,P<0.01)。MMP-1蛋白表达与星型胶质细胞瘤的恶性程度显著相关(tb=0.463,P<0.001)。随着胶质瘤病理分级增高,其MMP-1蛋白表达水平明显增加。
2非肿瘤脑组织、I～IV级星形细胞瘤组织中MMP-3蛋白的阳性表达率分别为25%、33%、45.5%、35%、75%,各组间MMP-3的表达无显著性差异(X2=20.476,P=0.059)。然而,MMP-3蛋白表达与星型胶质细胞瘤的恶性程度显著相关(tb=0.276,P=0.005)。在胶质瘤组,随着胶质瘤病理分级增高,其MMP-3蛋白表达水平呈递增趋势。
3非肿瘤脑组织、I～IV级星形细胞瘤组织中MMP-7蛋白的阳性表达率分别为37.5%、50%、77.3%、75%、100%,各组间MMP-7的表达有显著性差异(X2=29.779,P=0.003)。MMP-7蛋白表达与星型胶质细胞瘤的恶性程度显著相关(tb=0.416,P<0.001)。随着胶质瘤病理分级增高,其MMP-7蛋白表达水平明显增加。
4非肿瘤脑组织、I～IV级星形细胞瘤组织中MMP-9的阳性表达率分别为0%、66.7%、81.8%、80%、100%,各组间MMP-9的表达有显著性差异(X2=44.038,P<0.001)。MMP-9蛋白表达与星型胶质细胞瘤的恶性程度显著相关(tb=0.427,P<0.001)。随着胶质瘤病理分级增高,其MMP-9蛋白表达水平明显增加。
结论
正常脑组织、I～IV级星形细胞瘤组织中MMP-1、3、7和9蛋白的表达与星型细胞瘤的恶性程度显著相关,可能为判断该肿瘤的恶性程度、侵袭能力及预后的良好分子标志物。
第三部分星形细胞瘤中MMP-1、3、7、9 mRNA表达及相关性探讨方法
取星形细胞瘤新鲜组织39例和正常新鲜脑组织12例,所有组织在离体30分钟内置冻存管中,并立即置于液氮罐中,-80℃冷冻保存备用。以一步法RNA抽提试剂盒提取组织细胞总RNA。以反转录法获得cDNA第一链。采用TaqMan探针技术,以荧光实时定量聚合酶链式反应法(Real-time Quantitative Polymerase Chain Reaction,RQ-PCR),检测组织中MMPs和内参GAPDH mRNA的含量。以MMPs和内参GAPDH mRNA含量的比值(均数±标准差)作为评价MMPs表达水平的指标。采用t检验,统计分析星形细胞瘤病理分级各组与正常脑组织MMPs mRNA表达水平的差异,以P<0.05为有显著性差异。
结果
1星形细胞瘤组织中MMP-9 mRNA的相对表达量明显高于非肿瘤脑组织(p=0.038)。低分化肿瘤组织(Ⅲ-Ⅳ级)MMP-9 mRNA表达量与非肿瘤脑组织及高分化肿瘤组织(Ⅰ-Ⅱ级)间有显著性差异(分别为p<0.001,p=0.001),而高分化肿瘤组织与非肿瘤脑组织间MMP-9 mRNA表达量无显著性差异(p=0.417)。
2 MMP-1、MMP-3 mRNA相对表达量在低分化肿瘤组织(Ⅲ-Ⅳ级)与高分化肿瘤组织(Ⅰ-Ⅱ级)及非肿瘤脑组织中变化较大,之间无显著性差异(分别为p=0.26, p=0.419)。
结论
1低分化星形细胞瘤组织(Ⅲ-Ⅳ级)中MMP-9 mRNA表达量明显高于正常脑组织及高分化肿瘤组织。MMP-9 mRNA表达检测可用来判断星形细胞瘤的恶性程度及预后。
2 MMP-1、MMP-3 mRNA表达量在非脑肿瘤组织和星形细胞瘤组织间无显著性差异,其检测对星形细胞瘤生物学行为的判断无显著意义。
总之,本研究表明,MMP-1-1607 2G/1G和MMP-7-181A/G基因多态性可能与成人星形细胞瘤的发生有关,并可单独或与其他基因多态性联合作为筛选星形细胞瘤高危个体的分子标志物。MMP-1、3、7和9蛋白的高表达可作为判断星形细胞瘤疾病进展和不良预后的指标。MMP-9 mRNA检测则可用于星形细胞瘤恶性程度的判定。
Objectives: Matrix metalloproteinases (MMPs), a family of highly conserved zinc-dependent proteolytic enzymes that degrade many different components of extracellular matrix (ECM) and regulate various cell behaviors, play important roles in tumor development, infiltration, and metastasis. It has been shown that MMPs expression is very low in normal tissues while elevates in tumor tissues with different extent. Growing evidence indicates that single nucleotide polymorphisms (SNPs) in promoters of MMP genes may result in variable transcription and expression of MMPs in different individuals, therefore, influence the development, progression, and outcome of tumors. Gliomas are the commonest primary brain tumors. Despite recent advances in diagnostic imaging, neurosurgical technique, radiation therapy, and chemotherapy, significant improvement in the survival of gliomas has not been achieved. Astrocytoma is the commonest type of brain gliomas and develops from a type of star-shaped cell called astrocyte. The etiology of astrocytoma is unknown. Although high-dose of radiotherapy and chemotherapy are supposed to be exogenous environmental causes, the accumulated data suggests that genetic background also play a role in the development of this tumor. Since it has been reported that the expression of MMP proteins may increase in astrocytoma tissues, we suspected that the SNPs in promoter region of MMP genes may alter susceptibility to astrocytoma via modifying the transcription activity of MMP genes. Recently, McCready et al. reported that the MMP-1 2G/1G SNP may play a role in the development and infiltration of glioblastoma, however, the association between the development of gloma and other MMP polymorphisms has not been reported so far. In addition, the relationship between the MMP polymorphisms and protein expression and mRNA transcription has not been clearly demonstrated. Hence, we conducted a hospital-based case control study on association between the promoter polymorphisms of MMP-1, 3, 7, 9 genes and susceptibility to adult astrocytoma. Additionally, the protein expression and mRNA transcription of the MMP-1, 3, 7, 9 were also evaluated in astrocytoma tumor tissues. This pilot study aims to investigate the relationship between the MMP-1, 3, 7, 9 genes and development and progression of astrocytoma, to help exploring the genetic liability as well as the molecular mechanism of the astrocytoma and provide candidate targets for prevention and control of this tumor type.
Part I Polymorphisms in the MMP-1,3,7,9 promoters and susceptibility to adult astrocytoma
Methods
The association between the promoter polymorphisms of MMP-1, 3, 7, 9 genes and susceptibility to adult astrocytoma was tested in a hospital-based case control study. Tissues from 236 cases of adult astrocytoma patients were collected after pathologic diagnosis for extracting DNAs by proteinase K digestion followed by phenol-chloroform purification. Blood samples from 366 healthy subjects were collected for DNA extraction by proteinase K digestion followed by a salting out procedure. The MMP-1 -1607 2G/1G, MMP-3 -1171 5A/6A, MMP-7 -181A/G, and MMP-9 -1562 C/T genotypes were determined by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) assay. Hardy-Weinberg analysis was performed to compare the observed and expected genotype frequencies using Chi-square test. Comparison of the MMP genotype distribution among study groups was performed by means of two-sided contingency tables using Chi-square test or Fisher’s exact test. The odds ratio (OR) and 95% confidence interval (CI) were calculated using an unconditional logistic regression model and adjusted by age and sex accordingly.
Results
1 The overall distribution of the MMP-1 1607 2G/1G SNP allelotype and genotype among astrocytoma patients and healthy controls was significantly different (P=0.002 and P<0.001, respectively). Compared with 2G/2G, the 1G/1G genotype significantly decreased the risk of development of astrocytoma, the age and gender adjusted OR was 0.58 (95%CI=0.42~0.79), while the relationship between the 2G/1G genotype and astrocytoma was not observed (age and gender adjusted OR was 0.74, 95%CI=0.51~1.08). The similar results were obtained when stratified by gender and age at tumor diagnosis (≤45 Years or > 45 Years). When stratified according to the World Health Organization (WHO) astrocytoma classification, the 2G/2G genotype significantly reduced the risk of grade II and III astrocytoma, the age and gender adjusted OR was 0.61(95%CI=0.40~0.93) and 0.41(95%CI=0.20~0.85), respectively, while correlation between the MMP-1 SNP and susceptibility to grade I and IV astrocytoma was not demonstrated.
2 The overall genotype and allelotype distribution among astrocytoma patients was not significantly different from that among healthy controls(P>0.05). Compared with 6A/6A, the most common genotype in the study population, both of the 5A/6A and 5A/5A genotype did not influence the risk of astrocytoma development, the age and gender adjusted OR was 1.09(95% CI=0.75~1.57) and 0.95 (95% CI=0.54~1.69), respectively. When stratified by gender, age at tumor diagnosis, and the WHO astrocytoma classification, association between the MMP-3 SNP and susceptibility to astrocytoma was also not observed.
3 The overall distribution of the MMP-7 -181 A/G SNP genotypes among astrocytoma patients and healthy controls was significantly different (P = 0.001). Compared with the A/A genotype, the G/G genotype significantly increased the risk to the development of astrocytoma, the age and gender adjusted odds ratio was 2.77 (95% CI = 1.27~6.02), while the MMP-7 A/G genotype also marginally increased the risk of developing astrocytoma (the adjusted OR = 1.69, 95% CI = 1.01~2.84). Stratification analysis showed that the MMP-7 G/G genotype significantly increased the risk of astrocytoma among individuals younger than 45 years compared with the A/A genotype (adjusted OR = 3.16, 95% CI = 1.09~9.16), however, the G/G genotype did not modify the risk of the occurrence of astrocytoma among people older than 45 years (adjusted OR = 1.93, 95% CI = 0.61~6.20). In addition, stratification analysis indicated that the MMP-7 G/G genotype significantly increased the risk of astrocytoma among male subjects (adjusted OR = 3.24, 95% CI = 1.12~9.41). Stratification analysis according to the WHO pathological grading showed that of astrocytomas. A significant higher risk of developing grade II astrocytoma was observed among individuals harboring the MMP-7 A/G genotype compared with those harboring the A/A genotype (adjusted OR = 2.06, 95% CI = 1.05~4.05). In addition, the G/G genotype significantly increased the risk of developing grades II, III, and IV astrocytoma compared with the A/A genotype, the adjusted odds ratio was 2.95 (95% CI = 1.21~7.17), 3.32 (95% CI = 1.15~9.61), and 3.25 (95% CI = 1.10~9.62), respectively, whereas the distribution different among patients with grade I astrocytoma and healthy controls was not observed.
4 The overall MMP-9 genotype and allelotype distribution among astrocytoma patients was not significantly different from that among healthy controls(P value was 0.92 and 0.818, respectively). Compared with the C/C genotype, genotypes with the -1562 T allele (C/T +T/T) did not show significant influence on the risk of astrocytoma development (age and gender adjusted OR= 1.09, 95% CI = 0.73~1.64). Stratification by gender, age, and the WHO astrocytoma classification also did not show an association between the MMP-9 SNP and susceptibility to astrocytoma.
Conclusions
1 The overall analysis and stratification analysis according to gender, age at diagnosis, and histological grade suggested that, the MMP-3 -1171 5A/6A and the MMP-9 -1562 C/T SNPs could not modify the risk of the adult astrocytoma development.
2 The MMP-1-1607 2G/1G polymorphism significantly influenced the risk of adult astrocytoma. Compared with 2G/2G, the predominant genotype among the study population, individuals with the 1G/1G genotype significantly decreased the susceptibility to astrocytoma.
3 The MMP-7-181A/G polymorphism significantly influenced the risk of adult astrocytoma development. Individuals harboring the G allele (A/G and G/G genotypes) significantly increased the susceptibility to astrocytoma. This association was more significant among male and people younger than 45 years old.
Part II: Relationship between expression of MMP-1,3,7,9 and clinical pathology in adult astrocytoma
Methods
Paraffin embedded blocks of tumor tissues from 70 pathologic diagnosed and graded astrocytoma cases and of non-tumor tissues from eight brain trauma patients were selected for detecting protein expression. MMP-1, 3, 7, 9 proteins were detected by immunohistochemistry (IHC) using the S-P staining kit. The status of the MMP expressions among histological grading groups was compared using Chi-square test. The correlation of the MMP expression with the pathologic grading was tested by the Kendall’s tau-b method with the significance level of 5%.
Results
1 The MMP-1 protein expression rate among non-tumor tissues and grade I～IV astrocytoma tissues was 12.5%, 75%, 86%, 90%, 100%, respectively. The MMP-1 expression among the above five groups was significantly different (X2=28.204,P<0.01). The MMP-1 expression was significantly correlated with the disease progression(tb=0.463,P<0.001). Thus, the MMP-1 expression significantly increased with the histological grading.
2 The MMP-3 protein expression rate among non-tumor tissues and grade I～IV astrocytoma tissues was 25%, 33%, 45.5%, 35%, 75%, respectively. The MMP-3 expression among the above five groups was not significantly different (X2=20.476,P=0.059). However, the MMP-3 expression was significantly correlated with the disease progressionand significantly increased with the histological grading(tb=0.276,P=0.005).
3 The MMP-7 protein expression rate among non-tumor tissues and grade I～IV astrocytoma tissues was 37.5%, 50%, 77.3%, 75%, 100%, respectively.
The MMP-7 expression among the above five groups was not significantly different (X2=29.779,P=0.003). The MMP-7 expression was significantly correlated with the disease progression and significantly increased with the histological grading(tb=0.416,P<0.001).
4 The MMP-9 protein expression rate among non-tumor tissues and grade I～IV astrocytoma tissues was 0%, 66.7%, 81.8%, 80%, 100%, respectively. The MMP-9 expression among the above five groups was not significantly different (X2=44.038,P<0.001). The MMP-9 expression was significantly correlated with the disease progression and significantly increased with the histological grading(tb=0.427,P<0.001).
Conclusions
The MMP-1,3,7,9 protein expression was significantly correlated to the tumor differentiation and may be useful molecular markers to predicate the prognosis of astrocytoma. Part III Expression and significance of MMP-1,3,7,9 mRNA in astrocytoma
Methods
Tumor tissues from 39 astrocytoma cases and non-tumor brain tissues from 12 brain trauma patients were frozen in liquid nitrogen in 30 minutes after resection and stored in a -80℃refrigerator. Total cellular RNA was extracted from tested tissues using the one-step RNA extraction kit. The first cDNA strand was generated by a reverse transcription system. The MMP mRNA from tumor and non-tumor brain tissues was quantitatively detected by the real-time fluorescence quantitative polymerase chain reaction (RQ-PCR) and TaqMan probe technology, with GAPDH gene as an internal reference.
The MMPs mRNA expression level was calculated by the ratio of MMPs to GAPDH and expressed as mean±standard deviation. Student's T test was used to compare the mRNA expression between the pathologic groups with a significance level of 5%.
Results
1 The MMP-9 mRNA expression in tumor tissues of astrocytoma was significantly higher than that in non-tumor tissues (p=0.038). The MMP-9 mRNA expression in low differentiation tissues (pathologic gradeⅢ-Ⅳ) was significantly higher than that in both of the high differentiation tissues (pathologic gradeⅠ-Ⅱ) and non-tumor brain tissues ( P value was =0.001 and <0.001, respectively). However, the significant difference between the high differentiation group and non-tumor group was not observed.
2 The MMP-1, 3 mRNA expression among low differentiation tissues (pathologic gradeⅢ-Ⅳ),high differentiation tissues (pathologic gradeⅠ-Ⅱ), and non-tumor brain tissues was not significantly different ( P value was 0.26 and 0.419, respectively).
Conclusions
1 The MMP-9 mRNA expression in low differentiation tissues (histological gradeⅢ-Ⅳ) was significantly higher than that in both of the high differentiation tissues (pathologic gradeⅠ-Ⅱ) and non-tumor brain tissues, suggesting that detection of the MMP-9 mRNA may be used to estimate the tumor histological differentiation and disease prognosis.
2 The MMP-1 and MMP-3 mRNA expression among astrocytoma tissues was not significantly different from that in non-tumor brain tissues, indicating that detection of the MMP-1 and MMP-3 mRNA may be not applicable for estimating the biological behavior of astrocytoma.
In summary, this pilot study showes that the polymorphisms in promoter regions of the MMP-1, 7 genes are involved in the carcinogenesis of adult astrocytoma and may be used as molecular markers, alone or together with other polymorphic genes, to screen individuals those at risk to develop astrocytoma. The high expression of the MMP-1,3,7,9 proteins can be used as candidate markers to estimate the progression and prognosis of adult astrocytoma. Additionally, detection of the MMP-9 mRNA may be used as an indicator of malignant characteristics of astrocytoma.
引文
1 Parsons SL, Watson SA, Brown PD, et al. Matrix metalloproteinases. Br J Surg, 1997, 84(2): 160-166
2 Noe V, Fingleton B, Jacobs K, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci, 2001, 114(Pt1): 111-118
3 Powell WC, Fingleton B, Wilson CL, et al. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis . Curr Biol, 1999, 9(24): 1441-1447
4 Johansson N, Ahonen M, Kahari VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci, 2000, 57:5~15
5 Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2002, 2: 161~174
6 Hirata H, Naito K, Yoshihiro S, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter is associated with conventional renal cell carcinoma. Int J Cancer, 2003, 106: 372~374
7 Ghilardi G, Biondi ML, Caputo, et al. A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility. Clin Cancer Res, 2002, 8: 3820~3823
8 Hinoda Y, Okayama N, Takano N, et al. Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer, 2002, 102: 526~529
9 Giorgio Ghilardi, Maria Lrisa Biondi, Maddalena Erario, et al. Colorectal Carcinoma Susceptibility and Metastases Are Associated with Matrix Metalloproteinase-7 Promoter Polymorphisms. Clinical Chemistry, 2003, 49: 1940~1942
10 Kim JS, Park HY, Kwon JH, et al. The roles of stromelysin -1 and the gelatinase B gene polymorphism in stable angina. Yonsei Med J, 2002, 43: 473~481
11 Pollanen PJ, Karhunen PJ, Mikkelsson J, et al. Coronary arterycomplicated lesion area is related to functional polymorphism of matrix metalloproteinase 9 gene: an autopsy study. Arterioscler Thromb Vasc Biol, 2001, 21: 1446~1450
12 Ye S, Dhillon S, Turner SJ, et al. Invasiveness of cutaneous malignant melanoma is influenced by matrix metalloproteinase 1 gene polymorphism. Cancer Res, 2001, 61: 1296~1298
13 Kanamori Y, Matsushima M, Minaguchi T, et al. Correlation between expression of the matrix metalloproteinase-1 gene in ovarian cancers and an insertion/deletion polymorphism in its promoter region. Cancer Res, 1999, 59: 4225~4227
14 Matsumura S, Oue N, Nakayama H, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin Oncol, 2005, 131: 19~25
15 Ichimura K, Ohgaki H, Kleihues P, et al. Molecular pathogenesis of astrocytic tumours . J Neurooncol, 2004, 70(2): 137–160
16 Malmer B, Gr?nberg H, Bergenheim AT, et al. Familial aggregation aggregation of astrocytoma in northern Sweden: an epidemiological cohort study . Int J Cancer, 1999, 81(3): 366–370
17 Wiemels JL, Wiencke JK, Patoka J, et al. Reduced immunoglobulin E and allergy among adults with glioma compared with controls . Cancer Res, 2004, 64(22): 8468–8473
18 McCready J, Broaddus WC, Sykes V, et al. Association of a single nucleotide polymorphism in the matrix metalloproteinase-1 promoter with glioblastoma. Int J Cancer. 2005 Dec 10;117(5):781-5
19 Miller SA, Dybes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res, 1988, 16: 1215
20 Zhu Y, Spitz MR, Lei L, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res, 2001, 61: 7825~7829
21 Gnasso A, Motti C, Irace C, et al. Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects. Arterioscler Thromb Vasc Biol, 2000, 20: 1600~1605
22 Ferrand PE, Parry S, Sammel M, et al. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. Mol Hum Reprod, 2002, 8: 494~501
23 Tower GB, Coon CI, Brinckerhoff CE. The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to high levels of MMP-1 transcription in MCF-7/ADR breast cancer cells. Breast Cancer Res Treat. 2003 Nov;82(2):75-82
24 Nishioka Y, Sagae S, Nishikawa A, et al. A relationship between Matrix metalloproteinase-1 (MMP-1) promoter polymorphism and cervical cancer progression. Cancer Lett. 2003 Oct 8;200(1):49-55
25 Kanamori Y, Matsushima M, Minaguchi T, et al. Correlation between expression of the matrix metalloproteinase-1 gene in ovarian cancers and an insertion/deletion polymorphism in its promoter region. Cancer Res. 1999 Sep 1;59(17):4225-7
26 Hinoda Y, Okayama N, Takano N, et al. Association of functional polymorphisms of matrix metalloproteinase MMP-1 and MMP-3 genes with colorectal cancer. Int J Cancer, 2002,102(5): 526-529
27 Ghilardi G, Biondi ML, Caputo M, et al. A single Nucleotide Polymorphism in the Matrix metalloproteinase-3 Promoter Enhances Breast Cancer Susceptibility.Clin Cancer Res, 2002,8(12): 3820-3823
28 Fang S, Jin X, Wang R, et al. Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China . Carcinogenesis, 2005, 26(2): 481-486
29 Zhang J, Jin X, Fang S, et al. The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastases in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma . Carcinogenesis, 2004, 25(12): 2519-2524
30 Li Y, Jin X, Kang S, et al. Polymorphisms in the promoter regions of the matrix metalloproteinases-1, -3, -7, and -9 and the risk of epithelial ovarian cancer in China . Gynecol Oncol, 2006, 101(1): 92-96
31 Zhang J, Jin X, Fang S, et al. The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma . Carcinogenesis, 2005, 26(10): 1748-1753
32 Jormsjo S, Whatling C, Walter DH, et al. Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients . Arterioscler Thromb Vasc Biol, 2001, 21(11): 1834-1839
33 Noe V, Fingleton B, Jacobs K, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1 . J Cell Sci, 2001, 114(Pt1): 111-118
34 Powell WC, Fingleton B, Wilson CL, et al. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis . Curr Biol, 1999, 9(24): 1441-1447
35 Barille S, Bataille R, Rapp MJ, et al. Production of metalloproteinase-7 (matrilysin) by human myeloma cells and its potential involvement in metalloproteinase-2 activation . J Immunol, 1999, 163(10): 5723-5728
36 Morgan AR, Zhang B, Tapper W,et al. Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease. J Mol Med, 2003, 81: 321~326
37 Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol., 2001, 17: 463~516
38 Grieu F, Li WQ, Iacopetta B. Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype. Breast Cancer Res Treat, 2004, 88(3): 197-204
39 Matsumura S, Oue N, Nakayama H, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin Oncol, 2005, 131(1): 19-25
40 Wang YM, et al. (correspondence author) No association between the C-1562T polymorphism in the promoter of matrix metalloproteinase-9 gene and non-small cell lung carcinoma. Lung Cancer, 2005;49:155-61
41 Ferrand PE, Parry S, Sammel M, et al. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. Mol Hum Reprod, 2002, 8: 494~501
1 Nakada M, Okada Y, Yamashita J. The role of matrix metalloproteinases in glioma invasion. Front Biosci, 2003,8:e261-9
2 VanMeter TE, Rooprai HK, Kibble MM, et al. The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol, 2001,53:213-35
3 Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer, 2003,3:489-501
4 Kunishio K, Okada M, Matsumoto Y, et al. Matrix metalloproteinase-2 and -9 expression in astrocytic tumors. Brain Tumor Pathol, 2003,20:39-45
5 Choe G, Park JK, Jouben-Steele L, et al. Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype. Clin Cancer Res, 2002,8:2894-901
6 Komatsu K, Nakanishi Y, Nemoto N, et al. Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas. Brain Tumor Pathol, 2004,21:105-12
7 Kondraganti S, Mohanam S, Chintala SK, et al. Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. Cancer Res, 2000,60:6851-5
8 Lakka SS, Gondi CS, Yanamandra N, et al. Synergistic down-regulation of urokinase plasminogen activator receptor and matrix metalloproteinase-9 in SNB19 glioblastoma cells efficiently inhibits glioma cell invasion, angiogenesis, and tumor growth. Cancer Res, 2003,63:2454-61
9 Lakka SS, Rajan M, Gondi C, et al. Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene, 2002,21:8011-9
10 Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2),gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer, 1999,79:1828-35
11 Raithatha SA, Muzik H, Muzik H, et al. Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas. Neuro-oncol, 2000,2:145-50
12 Vince GH, Wagner S, Pietsch T, et al. Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. Int J Dev Neurosci, 1999,17:437-45
13 Platten M, Wick W, Weller M. Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape. Microsc Res Tech, 2001,52:401-10
14 于士柱, 浦佩玉. 血小板源生长因子旁分泌效应与胶质瘤间质血管反应性增 …. 中华神经外科杂志, 2000,16:183-186
15 Sato Y, Abe M, Tanaka K, et al. Signal transduction and transcriptional regulation of angiogenesis. Adv Exp Med Biol, 2000,476:109-15
16 Rome C, Arsaut J, Taris C, et al. MMP-7 (matrilysin) expression in human brain tumors. Mol Carcinog, 2007
17 Ii M, Yamamoto H, Adachi Y, et al. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood), 2006,231:20-7
18 Takeuchi N, Ichikawa Y, Ishikawa T, et al. Matrilysin gene expression in sporadic and familial colorectal adenomas. Mol Carcinog, 1997,19:225-9
19 Thorns V, Walter GF, Thorns C. Expression of MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11 in human astrocytic and oligodendroglial gliomas. Anticancer Res, 2003,23:3937-44
20 李树合,周定标,余新光,等. 胶质母细胞瘤中 MMPs 和 TIMPs 的表达 及 其 与 瘤 周 水 肿 的 相 关 性 分 析 . 军 医 进 修 学 院 学 报 ,2006,27:214-215
21 刘锦平,黄书岚,刘仁忠. 基质金属蛋白酶-2、-7、-9 在人脑星形细胞瘤中的表达及临床意义. 卒中与神经疾病, 2003,10:291-293
22 The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell. 1999 Jul 23;98(2):137-46
23 Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer, 2000,36:1621-30
24 王爱民, 华川. 食管癌患者基质分解素-1 基因表达的研究. 中国肿瘤临床与康复, 2000,7:8-9
25 Bodey B, Bodey B Jr, Siegel SE, et al. Matrix metalloproteinase expression in childhood astrocytomas. Anticancer Res, 2000,20:3287-92
26 Mercapide J, Lopez De Cicco R, Castresana JS, et al. Stromelysin-1/matrix metalloproteinase-3 (MMP-3) expression accounts for invasive properties of human astrocytoma cell lines. Int J Cancer, 2003,106:676-82
27 Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol, 2001,17:463-516
28 Pardo A, Selman M. MMP-1: the elder of the family. Int J Biochem Cell Biol, 2005,37:283-8
29 Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev, 2004,23:101-17
30 Gupta GP, Nguyen DX, Chiang AC, et al. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature, 2007,446:765-70
1 Reifenberger G, Collins VP. Pathology and molecular genetics of astrocytic gliomas. J Mol Med, 2004,82:656-70
2 Bellail AC, Hunter SB, Brat DJ, et al. Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. Int J Biochem Cell Biol, 2004,36:1046-69
3 Chintala SK, Tonn JC, Rao JS. Matrix metalloproteinases and their biological function in human gliomas. Int J Dev Neurosci, 1999,17:495-502
4 Nakada M, Okada Y, Yamashita J. The role of matrix metalloproteinases in glioma invasion. Front Biosci, 2003,8:e261-9
5 VanMeter TE, Rooprai HK, Kibble MM, et al. The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol, 2001,53:213-35
6 Duffy MJ, Maguire TM, Hill A, et al. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res, 2000,2:252-7
7 Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med, 1993,4:197-250
8 Wang M, Wang T, Liu S, et al. The expression of matrix metalloproteinase-2 and -9 in human gliomas of different pathological grades. Brain Tumor Pathol, 2003,20:65-72
9 Rao JS, Yamamoto M, Mohaman S, et al. Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin Exp Metastasis, 1996,14:12-8
10 Lampert K, Machein U, Machein MR, et al. Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors. Am J Pathol, 1998,153:429-37
11 Raithatha SA, Muzik H, Muzik H, et al. Localization of gelatinase-Aand gelatinase-B mRNA and protein in human gliomas. Neuro-oncol, 2000,2:145-50
12 Sawaya R, Go Y, Kyritisis AP, et al. Elevated levels of Mr 92,000 type IV collagenase during tumor growth in vivo. Biochem Biophys Res Commun, 1998,251:632-6
13 Rao JS, Steck PA, Tofilon P, et al. Role of plasminogen activator and of 92-KDa type IV collagenase in glioblastoma invasion using an in vitro matrigel model. J Neurooncol, 1994,18:129-38
14 Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer, 1999,79:1828-35
15 Huang TS, Lee CC, Chang AC, et al. Shortening of microsatellite deoxy(CA) repeats involved in GL331-induced down-regulation of matrix metalloproteinase-9 gene expression. Biochem Biophys Res Commun, 2003,300:901-7
16 Kondraganti S, Mohanam S, Chintala SK, et al. Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. Cancer Res, 2000,60:6851-5
17 Rooprai HK, Rucklidge GJ, Panou C, et al. The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells. Br J Cancer, 2000,82:52-5
18 Kubiatowski T, Jang T, Lachyankar MB, et al. Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J Neurosurg, 2001,95:480-8
19 Chandrasekar N, Jasti S, Alfred-Yung WK, et al. Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions. Clin Exp Metastasis, 2000,18:337-42
20 Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol, 2001,17:463-516
21 Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer, 2003,3:489-501
22 Nabeshima K, Inoue T, Shimao Y, et al. Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int, 2002,52:255-64
23 Binder DK, Berger MS. Proteases and the biology of glioma invasion. J Neurooncol, 2002,56:149-58
24 Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer, 2000,36:1621-30
25 Bodey B, Bodey B Jr, Siegel SE, et al. Matrix metalloproteinase expression in childhood astrocytomas. Anticancer Res, 2000,20:3287-92
26 Matsuzawa K, Fukuyama K, Dirks PB, et al. Expression of stromelysin 1 in human astrocytoma cell lines. J Neurooncol, 1996,30:181-8
27 Ii M, Yamamoto H, Adachi Y, et al. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood), 2006,231:20-7
28 Nosho K, Yamamoto H, Taniguchi H, et al. Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis. Clin Cancer Res, 2004,10:7950-7
29 Shigemasa K, Tanimoto H, Sakata K, et al. Induction of matrix metalloprotease-7 is common in mucinous ovarian tumors including early stage disease. Med Oncol, 2000,17:52-8
30 Thorns V, Walter GF, Thorns C. Expression of MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11 in human astrocytic andoligodendroglial gliomas. Anticancer Res, 2003,23:3937-44
31 Rome C, Arsaut J, Taris C, et al. MMP-7 (matrilysin) expression in human brain tumors. Mol Carcinog, 2007
1 Vu TH, Shipley JM, Bergers G, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell, 1998,93:411-22
2 Kleiner DE, Stetler-Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol, 1999,43 Suppl:S42-51
3 GROSS J, LAPIERE CM. Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci U S A, 1962,48:1014-22
4 Puente XS, Sanchez LM, Overall CM, et al. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet, 2003,4:544-58
5 Kahari VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med, 1999,31:34-45
6 Van Wart HE, Birkedal-Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A, 1990,87:5578-82
7 Hamasuna R, Kataoka H, Moriyama T, et al. Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP. Int J Cancer, 1999,82:274-81
8 Wilson MJ, Sellers RG, Wiehr C, et al. Expression of matrix metalloproteinase-2 and -9 and their inhibitors, tissue inhibitor of metalloproteinase-1 and -2, in primary cultures of human prostatic stromal and epithelial cells. J Cell Physiol, 2002,191:208-16
9 Kugler A. Matrix metalloproteinases and their inhibitors. Anticancer Res, 1999,19:1589-92
10 Uhm JH, Dooley NP, Villemure JG, et al. Glioma invasion in vitro: regulation by matrix metalloprotease-2 and protein kinase C. Clin Exp Metastasis, 1996,14:421-33
11 Kubiatowski T, Jang T, Lachyankar MB, et al. Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J Neurosurg, 2001,95:480-8
12 Westermarck J, Seth A, Kahari VM. Differential regulation of interstitial collagenase (MMP-1) gene expression by ETS transcription factors. Oncogene, 1997,14:2651-60
13 Qin H, Sun Y, Benveniste EN. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem, 1999,274:29130-7
14 Wagner S, Stegen C, Bouterfa H, et al. Expression of matrix metalloproteinases in human glioma cell lines in the presence of IL-10. J Neurooncol, 1998,40:113-22
15 Wiranowska M, Rojiani AM, Gottschall PE, et al. CD44 expression and MMP-2 secretion by mouse glioma cells: effect of interferon and anti-CD44 antibody. Anticancer Res, 2000,20:4301-6
16 Yamamoto M, Mohanam S, Sawaya R, et al. Differential expressionof membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro. Cancer Res, 1996,56:384-92
17 Oliver L, Tremblais K, Guriec N, et al. Influence of bcl-2-related proteins on matrix metalloproteinase expression in a rat glioma cell line. Biochem Biophys Res Commun, 2000,273:411-6
18 St-Pierre Y, Aoudjit F, Lalancette M, et al. Dissemination of T cell lymphoma to target organs: a post-homing event implicating ICAM-1 and matrix metalloproteinases. Leuk Lymphoma, 1999,34:53-61
19 Carmeliet P, Moons L, Lijnen R, et al. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet, 1997,17:439-44
20 Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol, 2001,17:463-516
21 Strongin AY, Collier I, Bannikov G, et al. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem, 1995,270:5331-8
22 Deryugina EI, Ratnikov B, Monosov E, et al. MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells. Exp Cell Res, 2001,263:209-23
23 Morrison CJ, Butler GS, Bigg HF, et al. Cellular activation of MMP-2 (gelatinase A) by MT2-MMP occurs via a TIMP-2-independent pathway. J Biol Chem, 2001,276:47402-10
24 Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci, 2002,115:3719-27
25 Greene J, Wang M, Liu YE, et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem, 1996,271:30375-80
26 Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta, 2000,1477:267-83
27 Edwards DR, Rocheleau H, Sharma RR, et al. Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases-1 (TIMP-1) transcription. Biochim Biophys Acta, 1992,1171:41-55
28 Ahonen M, Baker AH, Kahari VM. Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells. Cancer Res, 1998,58:2310-5
29 Bond M, Murphy G, Bennett MR, et al. Localization of the death domain of tissue inhibitor of metalloproteinase-3 to the N terminus. Metalloproteinase inhibition is associated with proapoptotic activity. J Biol Chem, 2000,275:41358-63
30 Bachmeier BE, Albini A, Vene R, et al. Cell density-dependent regulation of matrix metalloproteinase and TIMP expression in differently tumorigenic breast cancer cell lines. Exp Cell Res, 2005,305:83-98
31 Celentano DC, Frishman WH. Matrix metalloproteinases and coronary artery disease: a novel therapeutic target. J Clin Pharmacol, 1997,37:991-1000
32 Lochter A, Sternlicht MD, Werb Z, et al. The significance of matrix metalloproteinases during early stages of tumor progression. Ann N Y Acad Sci, 1998,857:180-93
33 Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst, 1997,89:1260-70
34 Nelson AR, Fingleton B, Rothenberg ML, et al. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol, 2000,18:1135-49
35 Curran S, Murray GI. Matrix metalloproteinases: molecular aspects oftheir roles in tumour invasion and metastasis. Eur J Cancer, 2000,36:1621-30
36 McCawley LJ, Matrisian LM. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today, 2000,6:149-56
37 Vihinen P, Kahari VM. Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer, 2002,99:157-66
38 Murawaki Y, Ikuta Y, Okamoto K, et al. Plasma matrix metalloproteinase-9 (gelatinase B) in patients with hepatocellular carcinoma. Res Commun Mol Pathol Pharmacol, 2000,108:351-7
39 Hayasaka A, Suzuki N, Fujimoto N, et al. Elevated plasma levels of matrix metalloproteinase-9 (92-kd type IV collagenase/gelatinase B) in hepatocellular carcinoma. Hepatology, 1996,24:1058-62
40 Endo K, Maehara Y, Baba H, et al. Elevated levels of serum and plasma metalloproteinases in patients with gastric cancer. Anticancer Res, 1997,17:2253-8
41 Murray GI, Duncan ME, O'Neil P, et al. Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J Pathol, 1998,185:256-61
42 Kawamata H, Kameyama S, Kawai K, et al. Marked acceleration of the metastatic phenotype of a rat bladder carcinoma cell line by the expression of human gelatinase A. Int J Cancer, 1995,63:568-75
43 Tsunezuka Y, Kinoh H, Takino T, et al. Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Res, 1996,56:5678-83
44 Powell WC, Knox JD, Navre M, et al. Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. Cancer Res, 1993,53:417-22
45 Wilson CL, Heppner KJ, Labosky PA, et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A, 1997,94:1402-7
46 Itoh T, Tanioka M, Yoshida H, et al. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res, 1998,58:1048-51
47 Martin DC, Fowlkes JL, Babic B, et al. Insulin-like growth factor II signaling in neoplastic proliferation is blocked by transgenic expression of the metalloproteinase inhibitor TIMP-1. J Cell Biol, 1999,146:881-92
48 Manes S, Mira E, Barbacid MM, et al. Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3. J Biol Chem, 1997,272:25706-12
49 Nosho K, Yamamoto H, Taniguchi H, et al. Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis. Clin Cancer Res, 2004,10:7950-7
50 Shigemasa K, Tanimoto H, Sakata K, et al. Induction of matrix metalloprotease-7 is common in mucinous ovarian tumors including early stage disease. Med Oncol, 2000,17:52-8
51 Shoji A, Sakamoto Y, Tsuchiya T, et al. Inhibition of tumor promoter activity toward mouse fibroblasts and their in vitro transformation by tissue inhibitor of metalloproteinases-1 (TIMP-1). Carcinogenesis, 1997,18:2093-100
52 Kruger A, Sanchez-Sweatman OH, Martin DC, et al. Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line. Oncogene, 1998,16:2419-23
53 Koop S, Khokha R, Schmidt EE, et al. Overexpression of metalloproteinase inhibitor in B16F10 cells does not affect extravasation but reduces tumor growth. Cancer Res, 1994,54:4791-7
54 Henriet P, Blavier L, Declerck YA. Tissue inhibitors of metalloproteinases (TIMP) in invasion and proliferation. APMIS, 1999,107:111-9
55 Bramhall SR, Neoptolemos JP, Stamp GW, et al. Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. J Pathol, 1997,182:347-55
56 Fong KM, Kida Y, Zimmerman PV, et al. TIMP1 and adverse prognosis in non-small cell lung cancer. Clin Cancer Res, 1996,2:1369-72
57 Karameris A, Panagou P, Tsilalis T, et al. Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas. A molecular and immunohistochemical study. Am J Respir Crit Care Med, 1997,156:1930-6
58 McCarthy K, Maguire T, McGreal G, et al. High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer. Int J Cancer, 1999,84:44-8
59 Vince GH, Wagner S, Pietsch T, et al. Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. Int J Dev Neurosci, 1999,17:437-45
60 Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer, 1999,79:1828-35
61 Fang J, Shing Y, Wiederschain D, et al. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci U S A, 2000,97:3884-9
62 Sounni NE, Roghi C, Chabottaux V, et al. Up-regulation of vascular endothelial growth factor-A by active membrane-type 1 matrix metalloproteinase through activation of Src-tyrosine kinases. J Biol Chem, 2004,279:13564-74
63 Weinrach DM, Wang KL, Wiley EL, et al. Immunohistochemical expression of matrix metalloproteinases 1, 2, 9, and 14 in dermatofibrosarcoma protuberans and common fibrous histiocytoma (dermatofibroma). Arch Pathol Lab Med, 2004,128:1136-41
64 Huang TS, Lee CC, Chang AC, et al. Shortening of microsatellite deoxy(CA) repeats involved in GL331-induced down-regulation of matrix metalloproteinase-9 gene expression. Biochem Biophys Res Commun, 2003,300:901-7
65 van den Oord JJ, Paemen L, Opdenakker G, et al. Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. Am J Pathol, 1997,151:665-70
66 Zhou KX, Wu BQ, Zheng J. Effects of metalloproteinases-1 (TIMP-1) cDNA transfection on biological behaviors of PG cells. Zhonghua Yi Xue Za Zhi, 1994,74:402-5, 454
67 李红梅, 方伟岗. TIMP-2 基因转染对高转移性人巨细胞肺癌细胞系生物学行为的影响. 中华医学杂志, 1997,77:652-656
68 牛桂莲, 方伟岗. TIMP-3 基因转染抑制人肺癌细胞系侵袭与转移的研究. 中华病理学杂志, 1998,27:421-424
69 李红梅, 方伟岗. 不同转移潜能的人肿瘤细胞系金属蛋白酶活性分析. 中华病理学杂志, 1998,27:341-343
70 Murphy AN, Unsworth EJ, Stetler-Stevenson WG. Tissue inhibitor of metalloproteinases-2 inhibits bFGF-induced human microvascular endothelial cell proliferation. J Cell Physiol, 1993,157:351-8
71 Brookes AJ. The essence of SNPs. Gene, 1999,234:177-86
72 Lai E. Application of SNP technologies in medicine: lessons learned and future challenges. Genome Res, 2001,11:927-9
73 Sachidanandam R, Weissman D, Schmidt SC, et al. A map of human genome sequence variation containing 1.42 million single nucleotidepolymorphisms. Nature, 2001,409:928-33
74 Chasman D, Adams RM. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J Mol Biol, 2001,307:683-706
75 Rutter JL, Mitchell TI, Buttice G, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res, 1998,58:5321-5
76 Wyatt CA, Coon CI, Gibson JJ, et al. Potential for the 2G single nucleotide polymorphism in the promoter of matrix metalloproteinase to enhance gene expression in normal stromal cells. Cancer Res, 2002,62:7200-2
77 Tower GB, Coon CI, Brinckerhoff CE. The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to high levels of MMP-1 transcription in MCF-7/ADR breast cancer cells. Breast Cancer Res Treat, 2003,82:75-82
78 Nishioka Y, Sagae S, Nishikawa A, et al. A relationship between Matrix metalloproteinase-1 (MMP-1) promoter polymorphism and cervical cancer progression. Cancer Lett, 2003,200:49-55
79 Hirata H, Naito K, Yoshihiro S, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter is associated with conventional renal cell carcinoma. Int J Cancer, 2003,106:372-4
80 Hinoda Y, Okayama N, Takano N, et al. Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer, 2002,102:526-9
81 Zhu Y, Spitz MR, Lei L, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res, 2001,61:7825-9
82 Tower GB, Coon CI, Brinckerhoff CE. The 2G single nucleotide polymorphism (SNP) in the MMP-1 promoter contributes to highlevels of MMP-1 transcription in MCF-7/ADR breast cancer cells. Breast Cancer Res Treat, 2003,82:75-82
83 Nishioka Y, Sagae S, Nishikawa A, et al. A relationship between Matrix metalloproteinase-1 (MMP-1) promoter polymorphism and cervical cancer progression. Cancer Lett, 2003,200:49-55
84 Hirata H, Naito K, Yoshihiro S, et al. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter is associated with conventional renal cell carcinoma. Int J Cancer, 2003,106:372-4
85 Hinoda Y, Okayama N, Takano N, et al. Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer, 2002,102:526-9
86 McCready J, Broaddus WC, Sykes V, et al. Association of a single nucleotide polymorphism in the matrix metalloproteinase-1 promoter with glioblastoma. Int J Cancer, 2005,117:781-5
87 Jin X, Kuang G, Wei LZ, et al. No association of the matrix metalloproteinase 1 promoter polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in northern China. World J Gastroenterol, 2005,11:2385-9
88 方淑梅,金霞,李琰,等. 基质金属蛋白酶 1 基因多态性与非小细胞肺癌的关系. 肿瘤, 2006,26:64-67
89 Zhang XP, Zhou FJ, Shen PF, et al. Significance of activated matrix metalloproteinase 2 (MMP2) in progression of bladder transitional cell carcinoma. Ai Zheng, 2003,22:637-9
90 Pesta M, Holubec L Jr, Topolcan O, et al. Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res, 2005,25:3387-91
91 Nakopoulou L, Tsirmpa I, Alexandrou P, et al. MMP-2 protein ininvasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival. Breast Cancer Res Treat, 2003,77:145-55
92 Yu C, Pan K, Xing D, et al. Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer. Cancer Res, 2002,62:6430-3
93 Miao X, Yu C, Tan W, et al. A functional polymorphism in the matrix metalloproteinase-2 gene promoter (-1306C/T) is associated with risk of development but not metastasis of gastric cardia adenocarcinoma. Cancer Res, 2003,63:3987-90
94 Vasku A, Goldbergova M, Holla LI, et al. Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure. Clin Chem Lab Med, 2003,41:1299-303
95 Hinoda Y, Okayama N, Takano N, et al. Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer, 2002,102:526-9
96 Ghilardi G, Biondi ML, Caputo M, et al. A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility. Clin Cancer Res, 2002,8:3820-3
97 Szyllo K, Smolarz B, Romanowicz-Makowska H, et al. The promoter polymorphism of the matrix metalloproteinase 3 (MMP-3) gene in women with ovarian cancer. J Exp Clin Cancer Res, 2002,21:357-61
98 Zhang J, Jin X, Fang S, et al. The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma. Carcinogenesis, 2004,25:2519-24
99 Fang S, Jin X, Wang R, et al. Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China. Carcinogenesis, 2005,26:481-6
100Liu PY, Chen JH, Li YH, et al. Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction. ThrombHaemost, 2003,90:132-9
101Ghilardi G, Biondi ML, DeMonti M, et al. Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosis. Stroke, 2002,33:2408-12
102Satsangi J, Chapman RW, Haldar N, et al. A functional polymorphism of the stromelysin gene (MMP-3) influences susceptibility to primary sclerosing cholangitis. Gastroenterology, 2001,121:124-30
103Knox JD, Boreham DR, Walker JA, et al. Mapping of the metalloproteinase gene matrilysin (MMP7) to human chromosome 11q21-->q22. Cytogenet Cell Genet, 1996,72:179-82
104Ghilardi G, Biondi ML, Erario M, et al. Colorectal carcinoma susceptibility and metastases are associated with matrix metalloproteinase-7 promoter polymorphisms. Clin Chem, 2003,49:1940-2
105Zhang J, Jin X, Fang S, et al. The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma. Carcinogenesis, 2005,26:1748-53
106Jormsjo S, Whatling C, Walter DH, et al. Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arterioscler Thromb Vasc Biol, 2001,21:1834-9
107Duffy MJ, Maguire TM, Hill A, et al. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res, 2000,2:252-7
108Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med, 1993,4:197-250
109Morgan AR, Zhang B, Tapper W, et al. Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease. J Mol Med, 2003,81:321-6
110Grieu F, Li WQ, Iacopetta B. Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype. Breast Cancer Res Treat, 2004,88:197-204
111Matsumura S, Oue N, Nakayama H, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin Oncol, 2005,131:19-25
112Morgan AR, Zhang B, Tapper W, et al. Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease. J Mol Med, 2003,81:321-6
113Wang Y, Fang S, Wei L, et al. No association between the C-1562T polymorphism in the promoter of matrix metalloproteinase-9 gene and non-small cell lung carcinoma. Lung Cancer, 2005,49:155-61
114Joos L, He JQ, Shepherdson MB, et al. The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet, 2002,11:569-76
115Sawaya RE, Yamamoto M, Gokaslan ZL, et al. Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin Exp Metastasis, 1996,14:35-42
116Wang M, Wang T, Liu S, et al. The expression of matrix metalloproteinase-2 and -9 in human gliomas of different pathological grades. Brain Tumor Pathol, 2003,20:65-72
117Raithatha SA, Muzik H, Muzik H, et al. Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas. Neuro-oncol, 2000,2:145-50
118Lampert K, Machein U, Machein MR, et al. Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors. Am J Pathol, 1998,153:429-37
119Takahashi M, Fukami S, Iwata N, et al. In vivo glioma growth requires host-derived matrix metalloproteinase 2 for maintenance of angioarchitecture. Pharmacol Res, 2002,46:155-63
120Le DM, Besson A, Fogg DK, et al. Exploitation of astrocytes by glioma cells to facilitate invasiveness: a mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator-plasmin cascade. J Neurosci, 2003,23:4034-43
121Rooprai HK, Rucklidge GJ, Panou C, et al. The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells. Br J Cancer, 2000,82:52-5
122Park MJ, Park IC, Hur JH, et al. Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells. Neurosci Lett, 2000,290:201-4
123Chandrasekar N, Jasti S, Alfred-Yung WK, et al. Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions. Clin Exp Metastasis, 2000,18:337-42
124Nakada M, Nakamura H, Ikeda E, et al. Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors. Am J Pathol, 1999,154:417-28
125Nakada M, Okada Y, Yamashita J. The role of matrix metalloproteinases in glioma invasion. Front Biosci, 2003,8:e261-9
126Belien AT, Paganetti PA, Schwab ME. Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter. J Cell Biol, 1999,144:373-84
127Mercapide J, Lopez De Cicco R, Castresana JS, et al. Stromelysin-1/matrix metalloproteinase-3 (MMP-3) expression accounts for invasive properties of human astrocytoma cell lines. Int J Cancer, 2003,106:676-82
128Bodey B, Bodey B Jr, Siegel SE, et al. Matrix metalloproteinase expression in childhood astrocytomas. Anticancer Res, 2000,20:3287-92
129Deryugina EI, Bourdon MA, Luo GX, et al. Matrix metalloproteinase-2 activation modulates glioma cell migration. J Cell Sci, 1997,110 ( Pt 19):2473-82
130Planchenault T, Costa S, Fages C, et al. Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: relation to invasion. Neurosci Lett, 2001,299:140-4
131Nakada M, Kita D, Futami K, et al. Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma. J Neurosurg, 2001,94:464-73
132Groft LL, Muzik H, Rewcastle NB, et al. Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas. Br J Cancer, 2001,85:55-63
133Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell, 1996,86:353-64
134杨小立,王茂德,刘守勋,等. 微血管密度和基质金属蛋白酶-9 的表达与胶质瘤病理分级的关系. 西安交通大学学报:医学版, 2004,25:459-462
135Munaut C, Noel A, Hougrand O, et al. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int J Cancer, 2003,106:848-55
136Deryugina EI, Soroceanu L, Strongin AY. Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. Cancer Res, 2002,62:580-8
137Platten M, Wick W, Weller M. Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape. Microsc Res Tech, 2001,52:401-10
138于士柱, 浦佩玉. 血小板源生长因子旁分泌效应与胶质瘤间质血管反应性增 …. 中华神经外科杂志, 2000,16:183-186
139Zeng ZS, Cohen AM, Guillem JG. Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis. Carcinogenesis, 1999,20:749-55
140Kong D, Li Y, Wang Z, et al. Inhibition of Angiogenesis and Invasion by 3,3'-Diindolylmethane Is Mediated by the Nuclear Factor-{kappa}B Downstream Target Genes MMP-9 and uPA that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer. Cancer Res, 2007,67:3310-9
141Sato Y, Abe M, Tanaka K, et al. Signal transduction and transcriptional regulation of angiogenesis. Adv Exp Med Biol, 2000,476:109-15
142Slaton JW, Inoue K, Perrotte P, et al. Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. Am J Pathol, 2001,158:735-43
