CD147和MMP-2在宫颈癌中的表达及相关性研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的宫颈癌是女性常见的恶性肿瘤之一,在全球妇女恶性肿瘤中居第二位,细胞外基质金属蛋白酶诱导因子(extracellulr matrix metalloproteinase inducer,CD147/EMMPRIN)是可以调节基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)的因子之一,本实验通过检测CD147、MMP-2在正常宫颈组织、宫颈上皮内瘤样变(cervical intraepithelial neoplasia,CIN)以及宫颈癌中的表达情况,分析二者与宫颈癌相关临床病理指标的联系,探讨上述指标在宫颈癌发生、发展、浸润、转移中的作用及相互关系,为宫颈癌的诊断和治疗提供一种新的有效指标。
     方法采用链霉菌抗生物素蛋白-过氧化物酶连结法(即S-P法)免疫组化方法(immunohistochemistry,IHC)检测20例正常宫颈组织、21例CIN组织、59例宫颈癌组织中CD147和MMP-2的表达情况。分析宫颈癌中CD147和MMP-2的表达与临床分期、组织学分级等临床病理指标的相关性,同时对两者在宫颈癌发展过程中的相互关系进行初步研究。
     结果
     1.CD147和MMP-2主要在肿瘤组织中表达,在正常组织中也有表达。
     2.CD147在正常宫颈组织、CIN、宫颈癌组织中的阳性表达率分别为30.0%,81.0%,91.5%,呈逐渐升高的趋势(P<0.05).其中,正常宫颈组与CIN组之间有显著性差异(P<0.05);正常宫颈组与宫颈癌组之间有显著性差异(P<0.05);CIN组与宫颈癌组之间有显著性差异(P<0.05)。
     3.MMP-2在正常宫颈组织、CIN、宫颈癌组织中的阳性表达率分别为15.0%,38.1%,80.0%,呈现逐渐升高的趋势(P<0.05)。其中,正常宫颈组与CIN组之间无差异显著性(P>0.05);正常宫颈组与宫颈癌组之间差异有显著性(P<0.05);CIN组与宫颈癌组之间有显著性差异(P<0.05)。
     4.在宫颈癌中,CD147蛋白表达阳性率在有淋巴结转移组高于无淋巴结转移组(x~2=4.138,P<0.05);宫颈癌中CD147的表达与年龄、分期、大体类型、分化程度、组织类型均无关(P>0.05)。
     5.在宫颈癌中,MMP-2蛋白表达阳性率在FIGO分期Ⅰ~Ⅱa期高于Ⅱb~Ⅳ期(x~2=9.423,P<0.05),有淋巴结转移组高于无淋巴结转移组(x~2=5.019,P<0.05);宫颈癌中MMP-2的表达与年龄、大体类型、分化程度、组织类型均无关(P>0.05)。
     6.宫颈癌组织中CD147与MMP-2之间呈正相关,相关系数r_s=0.283(P<0.05)。结论CD147和MMP-2在正常宫颈、CIN、宫颈癌中的表达呈逐渐升高趋势;在宫颈癌中,CD147的表达在有淋巴结转移者表达高于无淋巴结转移者;在宫颈癌中,MMP-2的表达在Ⅱb~Ⅳ期高于Ⅰ~Ⅱa期,在有淋巴结转移的宫颈癌病例表达高于无淋巴结转移者;CD147和MMP-2之间有协同作用;提示CD147和MMP-2在宫颈癌的浸润和转移方面起重要作用,联合检测CD147和MMP-2有可能是宫颈癌诊断的标志物和治疗的新靶点,是评估宫颈癌严重程度的新指标。
Objective Cervical cancer is a common malignancy among women,ranked second among in the world of women malignant tumors.Extracellulr matrix metalloproteinase inducer(CD147/EMMPRIN) is one of the molecules involved in regulating the expression of matrix metalloproteinases(MMPs).The goal of this study was to analyze the expression levels of CD 147 and MMP-2 in normal cervical tissue,cervical intraepithelial neoplasia(CIN) and cervical carcinoma,and to analyze its relationship with clinicopathological parameters of cervical cancer-related links to explore the above-mentioned target happened in cervical cancer development, invasion and metastasis,for the diagnosis and treatment of cervical cancer to provide a new and effective target.
     Methods Using streptavidin-biotin-protein - linked peroxidase method(ie,SP) immunohistochemical method to detec the expression of CD 147 and MMP-2 in 20 cases of normal cervical tissue,21 cases of CIN tissue,59 cases of cervical cancer. Analysis of cervical cancer in CD 147 and MMP-2 expression and clinical stage, histological grade and other clinicopathological parameters of relevance,at the same time the relationship between CD 147 and MMP-2 was studyed in the development of cervical cancer for a preliminary study.
     Results
     1.CD 147 and MMP-2 were expressed mainly in cancerous lesions,but also expressed in some normal tissues.
     2.Positive expression rate of CD 147 in normal cervical tissues,CIN,cervical cancer tissues were 30.0%,81.0%,91.5%,the trend has gradually increased(P<0.05). Among them,significant difference was existed between normal cervical group and CIN group(P<0.05),also between normal cervical group and cancer group(P<0.05), CIN group and cancer group(P<0.05).
     3.Positive expression rate of MMP-2 in normal cervical tissues,CIN,cervical cancer tissues were 15.0%,38.1%,80.0%,the trend has gradually increased(P<0.05). Among them,significant difference was existed between normal cervical group and cancer group(P<0.05),also between CIN group and cancer group(P<0.05).There was no significant difference between normal cervical group and CIN group (P>0.05).
     4.In cervical carcinoma,positive rate of CD 147 protein expression with lymph node metastasis group was higher than that without lymph node metastasis group (x~2=4.138,P<0.05);Expression of CD147 in cervical cancer were not related with age,stage,gross type,the degree of differentiation,histological types(P>0.05).
     5.In cervical cancer,positive rate of MMP-2 protein's expression at FIGO stagesⅠ-Ⅱa period was higher than theⅡb-Ⅳperiod(x~2=9.423,P<0.05),there is lymph node metastasis group was higher than that without lymph node metastasis group(x~2=5.019,P<0.05);Expression of CD147 in cervical cancer were not related with age,gross type,the degree of differentiation,histological types(P>0.05).
     6.The relationship between CD 147 and MMP-2 was positively correlated,and the correlation coefficient rs = 0.283(P<0.05).
     Conclusion CD 147 and MMP-2 in the normal cervix,CIN,cervical carcinoma was higher trend;CD 147 in lymph node metastasis is higher than without lymph node metastasis.MMP-2 in the phaseⅡb-Ⅳ,there is lymph node metastasis of cases of cervical cancer is higher than theⅠ-Ⅱa period,no lymph node metastasis;There is synergy between CD 147 and MMP-2;CD 147 and MMP-2 plays an important role in cervical cancer invasion and metastasis,Combined detection of CD 147 and MMP-2 may be a new target of cancer diagnosis and treatment and a new way to assess the severity of cervical cancer.
引文
[1]Kobierski J,Emerich J,Krolikowska B,et al.Lymph node metastasis as a prognostic factor in cervical carcinoma[J].Ginekol Pol,2002,73(11):925-929.
    [2]Ellis S M,Nabeshima K,Biswas C.Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor[J].Cancer Res,1989,49(12):3385-3391.
    [3]Egeblad M,Werb Z.New functions for the matrix metalloproteinases in cancer progression[J].Nat Rev Cancer,2002,2(3):161-174.
    [4]Zhao H,Bernardo M M,Osenkowski P,et al.Differential inhibition of membrane type 3(MT3)-matrix metalloproteinase(MMP) and MT1-MMP by tissue inhibitor of metalloproteinase(TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation[J].J Biol Chem,2004,279(10):8592-8601.
    [5]王瑞年,朱延波,薛建元,等.胃癌浸润转移与整合蛋白、IV型胶原酶及细胞外基质的关系[J].中华病理学杂志,1994,13(5):278-281.
    [6]Davidson B,Goldberg I,Gotlieb W H,et al.Expression of matrix proteins in uterine cervical neoplasia using immunohistochemistry[J].Eur J Obstet Gynecol Reprod Biol,1998,76(1):109-114.
    [7]金波泉.细胞和分子免疫学[M].北京:科学出版社,2001:4.
    [8]Biswas C.Tumor cell stimulation of collagenase production by fibroblasts[J].Biochem Biophys Res Commun,1982,109(3):1026-1034.
    [9]Sidhu S S,Mengistab A T,Tauscher A N,et al.The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions[J].Oncogene,2004,23(4):956-963.
    [10]Sun J,Hemler M E.Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions[J].Cancer Res,2001,61(5):2276-2281.
    [11]Biswas C,Zhang Y,Decastro R,et al.The human tumor cell-derived collagenase stimulatory factor(renamed EMMPRIN) is a member of the immunoglobulin superfamily[J].Cancer Res,1995,55(2):434-439.
    [12]Tang Y,Kesavan P,Nakada M T,et al.Tumor-stroma interaction:positive feedback regulation of extracellular matrix metalloproteinase inducer(EMMPRIN)expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN[J].Mol Cancer Res,2004,2(2):73-80.
    [13]Hakomori S.Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism[J].Cancer Res,1996,56(23):5309-5318.
    [14]Nabeshima K,Iwasaki H,Koga K,et al.Emmprin(basigin/CD147):matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression[J].Pathol Int,2006,56(7):359-367.
    [15]Tang W,Hemler M E.Caveolin-1 regulates matrix metalloproteinases-1 induction and CD 147/EMMPRIN cell surface clustering[J].J Biol Chem,2004,279(12):11112-11118.
    [16]Guo H,Zucker S,Gordon M K,et al.Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells[J].J Biol Chem,1997,272(1):24-27.
    [17]Kataoka H,Decastro R,Zucker S,et al.Tumor cell-derived collagenase-stimulatory factor increases expression of interstitial collagenase,stromelysin,and 72-kDa gelatinase[J].Cancer Res,1993,53(13):3154-3158.
    [18]张惠忠,王梅,魏益平,等.非小细胞肺癌中EMMPRIN和HGF的表达及其对淋巴结转移和预后的影响[J].中国病理生理杂志,2007,23(9):1716-1719.
    [19]王善伟,陈丽荣.CD147、MMP-9和p—ERK在乳腺癌中的表达及临床意义[J].实用肿瘤杂志,2007,22(2):133-137.
    [20]张香梅,何常,张维元,等.结直肠癌中CD147、MMP-1表达及其临床病理意义[J].诊断病理学杂志,2008,15(2):124-126.
    [21]Jin J S,Hsieh D S,Loh S H,et al.Increasing expression of serine protease matriptase in ovarian tumors:tissue microarray analysis of immunostaining score with clinicopathological parameters[J].Mod Pathol,2006,19(3):447-452.
    [22]巫静娴,赵涌,贾世军,等.CD147与基质金属蛋白酶-2,3,9在卵巢癌中的表达及临床病理意义[J].重庆医科大学学报,2007,32(11):1165-1168.
    [23]Ueda K,Yamada K,Urashima M,et al.Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3[J].Oncol Rep,2007,17(4):731-735.
    [24]孟元光,魏丽惠,王建六.应用cDNA微阵列技术检测子宫内膜癌组织中基因表达图谱的变化[J].中华医学杂志,2001,81(11):665-668.
    [25]苑媛,李福琴,张璐,等.CD147和MMP-2在子宫内膜癌中的表达及意义[J].哈尔滨医科大学学报,2006,40(2):147-150.
    [26]Ju X Z,Yang J M,Zhou X Y,et al.EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer[J].Clin Cancer Res,2008,14(2):494-501.
    [27]Sier C F,Zuidwijk K,Zijlmans H J,et al.EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma[J].Int J Cancer,2006,118(12):2991-2998.
    [28]欧阳运薇,彭芝兰,姚先莹,等.基质金属蛋白酶-2和-9在宫颈癌的表达及其相关性研究[J].四川大学学报(医学版),2004,35(3):330-333.
    [29]陈旻静,武海龙.CD147、MMP-2和TIMP-2在皮肤鳞状细胞癌中的表达[J].基础医学与临床,2008,44(11):110-112.
    [30]Zucker S,Hymowitz M,Rollo E E,et al.Tumorigenic potential of extracellular matrix metalloproteinase inducer[J].Am J Pathol,2001,158(6):1921-1928.
    [31]Jia L,Wang H,Qu S,et al.CD147 regulates vascular endothelial growth factor-A expression,tumorigenicity,and chemosensitivity to curcumin in hepatocellular carcinoma[J].IUBMB Life,2008,60(1):57-63.
    [32]董敏,周仲文,赵仲华,等.非小细胞性肺癌中P-gp表达与CD147、MMPs表达的关系[J].复旦学报(医学版),2005,32(4):379-382.
    [33]Yang J M,Xu Z,Wu H,et al.Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells[J].Mol Cancer Res,2003,1(6):420-427.
    [34]黄宝成,商澎,骞爱荣,等.HAb18G/CD147拮抗肽的筛选及对肝癌细胞侵袭力的抑制[J].中华肿瘤杂志,2003,(2):111-114.
    [35]Lim M,Martinez T,Jablons D,et al.Tumor-derived EMMPRIN(extracellular matrix metalloproteinase inducer) stimulates collagenase transcription through MAPK p38[J].FEBS Lett,1998,441(1):88-92.
    [36]Jr Belton R J,Chen L,Mesquita F S,et al.Basigin-2 is a cell surface receptor for soluble basigin ligand[J].J Biol Chem,2008,283(26):17805-17814.
    [37]Davidson B,Givant-Horwitz V,Lazarovici P,et al.Matrix metalloproteinases (MMP),EMMPRIN(extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases(MAPK):co-expression in metastatic serous ovarian carcinoma[J].Clin Exp Metastasis,2003,20(7):621-631.
    [38]Tang Y,Nakada M T,Kesavan P,et al.Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases[J].Cancer Res,2005,65(8):3193-3199.
    [39]Berditchevski F,Chang S,Bodorova J,et al.Generation of monoclonal antibodies to integrin-associated proteins.Evidence that alpha3betal complexes with EMMPRIN/basigin/OX47/M6[J].J Biol Chem,1997,272(46):29174-29180.
    [40]Ahmed M I,Salahy E E,Tawfiq H,et al.Matrix metalloproteinase-2,squamous cell carcinoma antigen,and tissue polypeptide-specific antigen expression in Egyptian patients with cervical carcinoma:Relationship with prognosis[J].Dis Markers,2004,20(6):333-343.
    [41]俞薇薇,熊小亮,刘繁荣,等.CD147蛋白表达与子宫颈癌生物学行为的关系[J].中国妇幼保健,2008,23(21):2999-3002.
    [42]李海霞,唐峰,王文娟,等.耐药逆转剂对人乳腺癌细胞P-糖蛋白、EMMPRIN和MMP表达的影响[J].复旦学报(医学版),2008,35(4):498-503.
    [43]王永清,赵扬玉,江元慧,等.RNA干扰技术抑制EMMPRIN表达对人绒癌细胞JEG-3侵袭性的实验研究[J].中国优生与遗传杂志,2008,16(2):28-30.
    [44]张峰,刘晔,刘三光,等.PNA干预研究及其在肿瘤基因治疗中的应用[J].中华实验外科杂志,2006,23(3):381-382.
    [45]Elbashir S M,Harborth J,Lendeckel W,et al.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells[J].Nature,2001,411(6836):494-498.
    [46]Zou W,Yang H,Hou X,et al.Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion,tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910pm cells[J].Cancer Lett,2007,248(2):211-218.
    [47]Visse R,Nagase H.Matrix metalloproteinases and tissue inhibitors of metalloproteinases:structure,function,and biochemistry[J].Circ Res,2003,92(8):827-839.
    [48]郝力,丁美珍.宫颈癌患者基质金属蛋白酶2、9及其组织抑制剂检测的意义[J].浙江医学,2006,28(2):100-102.
    [49]李莉,刘少扬,江大琼.基质金属蛋白酶-2及其组织抑制物在宫颈癌中的表达[J].肿瘤,2004,31(2):123-125.
    [50]李敏,王文福,汪青.宫颈癌中MMP-2及TIMP-2的表达及其临床意义[J].解剖与临床,2004,9(4):241-243.
    [51]王冬,任宝红,王占东.MMP-2、CD44v6、端粒酶活性与宫颈癌的相关性研究[J].中国现代医学杂志,2003,13(20):21-24.
    [52]张永杰,彭素蓉,张彤.Ⅰ-Ⅱ期宫颈癌组织中CD44V6,MMP-2与VEGF-C蛋白的表达与预后的关系[J].实用癌症杂志,2005,20(4):371-373.
    [53]周彩云,姚济芬,陈晓端.基质金属蛋白酶MMP-2、9及其抑制因子TIMP-1、2在子宫颈鳞癌中表达的研究[J].癌症,2002,21(7):735-739.
    [54]石新兰,黎家华,胡余昌,等.p65及MMP-2、MMP-9、TIMP-2、TIMP-1在宫颈鳞癌的表达状态[J].肿瘤,2006,26(2):199-202.
    [55]张连郁,曹文枫,王耕辛.MMP-2和TIMP-2在宫颈腺癌中的表达及与其转移的关系[J].实用癌症杂志,2002,17(3):263-265.
    [56]Nasr M,Ayyad S B,E1-Lamie I K,et al.Expression of matrix metalloproteinase-2in preinvasive and invasive carcinoma of the uterine cervix[J].Eur J Gynaecol Oncol,2005,26(2):199-202.
    [57]Kato Y,Yamashita T,Ishikawa M.Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells[J].Oncol Rep,2002,9(3):565-569.
    [58]Brummer O,Bohmer G,Hollwitz B,et al.MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation-an immunohistochemical study[J].Gynecol Oncol,2002,84(2):222-227.
    [59]Sheu B C,Lien H C,Ho H N,et al.Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer[J].Cancer Res,2003,63(19):6537-6542.
    [60]Arguello-Ramirez J,Perez-Cardenas E,Delgado-Chavez R,et al.Matrix metalloproteinases-2,-3,and -9 secreted by explants of benign and malignant lesions of the uterine cervix[J].Int J Gynecol Cancer,2004,14(2):333-340.
    [61]Tsung A J,Kargiotis O,Chetty C,et al.Downregulation of matrix metalloproteinase-2(MMP-2) utilizing adenovirus-mediated transfer of small interfering RNA(siRNA) in a novel spinal metastatic melanoma model[J].Int J Oncol,2008,32(3):557-564.
    [62]谢涛,袁响林,于世英,等.RNA干扰HIF-1α降低宫颈癌细胞基质金属蛋白酶-2的表达[J].癌症,2008,27(6):600-605.
    [63]范懿隽,周家德.MMP-2及CD_(147)在宫颈上皮内瘤样病变组织中的表达及意义[J].山东医药,2008,48(2):62-63.
    [64]Yan L,Zucker S,Toole B P.Roles of the multifunctional glycoprotein,emmprin (basigin;CD147),in tumour progression[J].Thromb Haemost,2005,93(2):199-204.
    [65]朱军义,苑中甫.人宫颈鳞状细胞癌组织中细胞外基质金属蛋白酶诱导因子、基质金属蛋白酶-2蛋白的表达[J].郑州大学学报:医学版,2008,43(4):729-731.
    [66]Bordador L C,Li X,Toole B,et al.Expression of emmprin by oral squamous cell carcinoma[J].Int J Cancer,2000,85(3):347-352.
    [67]Kanekura T,Chen X,Kanzaki T.Basigin (CD 147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix met alloproteinases by fibroblasts[J].Int J Cancer,2002,99(4):520-528.
    [68]Deeg H J,Blazar B R,Bolwell B J,et al.Treatment of steroid-refractory acute graft-versus-host disease with anti-CD 147 monoclonal antibody ABX-CBL[J].Blood,2001,98(7):2052-2058.
    [1]金波泉.细胞和分子免疫学[M].北京:科学出版社,2001:4-7.
    [2]Biswas C.Tumor cell stimulation of collagenase production by fibroblasts[J].Biochem Biophys Res Commun,1982,109(3):1026-1034.
    [3]Sidhu S S,Mengistab A T,Tauscher A N,et al.The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions[J].Oncogene,2004,23(4):956-963.
    [4]Sun J,Hemler M E.Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions[J].Cancer Res,2001,61(5):2276-2281.
    [5]Ellis S M,Nabeshima K,Biswas C.Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor[J].Cancer Res,1989,49(12):3385-3391.
    [6]Biswas C,Zhang Y,Decastro R,et al.The human tumor cell-derived collagenase stimulatory factor(renamed EMMPRIN) is a member of the immunoglobulin superfamily[J].Cancer Res,1995,55(2):434-439.
    [7]Tang Y,Kesavan P,Nakada M T,et al.Tumor-stroma interaction:positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN[J].Mol Cancer Res,2004,2(2):73-80.
    [8]Hakomori S.Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism[J].Cancer Res,1996,56(23):5309-5318.
    [9]Tang W,Hemler M E.Caveolin-1 regulates matrix metalloproteinases-1induction and CD147/EMMPRIN cell surface clustering[J].J Biol Chem,2004,279(12):11112-11118.
    [10]Guo H,Zucker S,Gordon M K,et al.Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells[J].J Biol Chem,1997,272(1):24-27.
    [11]Kataoka H,Decastro R,Zucker S,et al.Tumor cell-derived collagenase-stimulatory factor increases expression of interstitial collagenase,stromelysin,and 72-kDa gelatinase[J].Cancer Res,1993,53(13):3154-3158.
    [12]张惠忠,王梅,魏益平,等.非小细胞肺癌中EMMPRIN和HGF的表达及其对淋巴结转移和预后的影响[J].中国病理生理杂志,2007,23(9):1716-1719.
    [13]王善伟,陈丽荣.CD147、MMP-9和p-ERK在乳腺癌中的表达及临床意义[J].实用肿瘤杂志,2007,22(2):133-137.
    [14]张香梅,何常,张维元,等.结直肠癌中CD147、MMP-1表达及其临床病理意义[J].诊断病理学杂志,2008,15(2):124-126.
    [15]Jin J S,Hsieh D S,Loh S H,et al.Increasing expression of serine protease matriptase in ovarian tumors:tissue microarray analysis of immunostaining score with clinicopathological parameters[J].Mod Pathol,2006,19(3):447-452.
    [16]巫静娴,赵涌,贾世军,等.CD147与基质金属蛋白酶-2,3,9在卵巢癌中的表达及临床病理意义[J].重庆医科大学学报,2007,32(11):1165-1168.
    [17]Ueda K,Yamada K,Urashima M,et al.Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3[J].Oncol Rep,2007,17(4):731-735.
    [18]孟元光,魏丽惠,王建六.应用cDNA微阵列技术检测子宫内膜癌组织中基因表达图谱的变化[J].中华医学杂志,2001,81(11):665-668.
    [19]苑嫒,李福琴,张璐,等.CD147和MMP-2在子宫内膜癌中的表达及意义[J].哈尔滨医科大学学报,2006,40(2):147-150.
    [20]Ju X Z,Yang J M,Zhou X Y,et al.EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer[J].Clin Cancer Res,2008,14(2):494-501.
    [21]Sier C F,Zuidwijk K,Zijlmans H J,et al.EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma[J].Int J Cancer,2006,118(12):2991-2998.
    [22]欧阳运薇,彭芝兰,姚先莹,等.基质金属蛋白酶-2和-9在宫颈癌的表达及其相关性研究[J].四川大学学报(医学版),2004,35(3):330-333.
    [23]陈旻静,武海龙.CD147、MMP-2和TIMP-2在皮肤鳞状细胞癌中的表达[J].基础医学与临床,2008,44(11):110-112.
    [24]Jia L,Wang H,Qu S,et al.CD147 regulates vascular endothelial growth factor-A expression,tumorigenicity,and chemosensitivity to curcumin in hepatocellular carcinoma[J].IUBMB Life,2008,60(1):57-63.
    [25]Zhao H,Bernardo M M,Osenkowski P,et al.Differential inhibition of membrane type 3(MT3)-matrix metalloproteinase(MMP) and MT1-MMP by tissue inhibitor of metalloproteinase(TIMP)-2 and TIMP-3 rgulates pro-MMP-2activation[J].J Biol Chem,2004,279(10):8592-8601.
    [26]董敏,周仲文,赵仲华,等.非小细胞性肺癌中P-gp表达与CD147、MMPs表达的关系[J].复旦学报(医学版),2005,32(4):379-382.
    [27]黄宝成,商澎,骞爱荣,等.HAb18G/CD147拮抗肽的筛选及对肝癌细胞侵袭力的抑制[J].中华肿瘤杂志,2003,(2):111-114).
    [28]Lim M,Martinez T,Jablons D,et al.Tumor-derived EMMPRIN(extracellular matrix metalloproteinase inducer) stimulates collagenase transcription through MAPK p38[J].FEBS Lett,1998,441(1):88-92.
    [29]Jr Belton R J,Chen L,Mesquita F S,et al.Basigin-2 is a cell surface receptor for soluble basigin ligand[J].J Biol Chem,2008,283(26):17805-17814.
    [30]Davidson B,Givant-Horwitz V,Lazarovici P,et al.Matrix metalloproteinases (MMP),EMMPRIN(extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases(MAPK):co-expression in metastatic serous ovarian carcinoma[J].Clin Exp Metastasis,2003,20(7):621-631.
    [31]Tang Y,Nakada M T,Kesavan P,et al.Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases[J].Cancer Res,2005,65(8):3193-3199.
    [32]Berditchevski F,Chang S,Bodorova J,et al.Generation of monoclonal antibodies to integrin-associated proteins.Evidence that alpha3betal complexes with EMMPRIN/basigin/OX47/M6[J].J Biol Chem,1997,272(46):29174-29180.
    [33]Sillanpaa S,Anttila M,Suhonen K,et al.Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 2 in epithelial ovarian cancer[J].Tumour Biol,2007,28(5):280-289.
    [34]张荣玲,曾杰,马丽,等.细胞外基质金属蛋白酶诱导因子与基质金属蛋白酶-2在卵巢肿瘤组织中的表达及意义[J].潍坊医学院学报,2007,29(2):120-122.
    [35]Zou w,Yang H,Hou X,et al.Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion,tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910pm cells[J].Cancer Lett,2007,248(2):211-218.
    [36]Davidson B,Goldberg I,Gotlieb W H,et al.Expression of matrix proteins in uterine cervical neoplasia using immunohistochemistry[J].Eur J Obstet Gynecol Reprod Biol,1998,76(1):109-114.
    [37]辛晓燕,邹伟,杨红,等.RNAi沉默CD147基因对卵巢癌细胞HO-8910pm生物学行为的影响[J].现代妇产科进展,2006,15(2):92-95.
    [38]周晓景,廖予妹,毕晓英,等.EMMPRIN、MMP-7在宫颈鳞癌组织中的表达及临床意义[J].肿瘤基础与临床,2008,21(3):195-197.
    [39]Zucker S,Hymowitz M,Rollo E E,et al.Tumorigenic potential of extracellular matrix metalloproteinase inducer[J].Am J Pathol,2001,158(6):1921-1928.
    [40]张峰,刘晔,刘三光,等.RNA干预研究及其在肿瘤基因治疗中的应用[J].中华实验外科杂志,2006,23(3):381-382.
    [41]Elbashir S M,Harborth J,Lendeckel W,et al.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells[J].Nature,2001,411(6836):494-498.
    [42]Bordador L C,Li X,Toole B,et al.Expression of emmprin by oral squamous cell carcinoma[J].Int J Cancer,2000,85(3):347-352.
    [43]Kanekura T,Chen X,Kanzaki T.Basigin(CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts[J].Int J Cancer,2002,99(4):520-528.
    [44]Deeg H J,Blazar B R,Bolwell B J,et al.Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL[J].Blood,2001,98(7):2052-2058.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700