MMP-7、TIMP-1、E-CAD、Syndecan-1与胃癌浸润、转移关系的研究
|
摘要
目的：粘附和降解是癌细胞浸润转移的两个关键步骤。MMP-7、TIMP-1与细胞外基质降解有关。E-CAD、Syndecan-1介导细胞-细胞(或基质)粘附。研究发现MMP-7可通过降解E-CAD破坏细胞连接。而Syndecan-1的表达与E-CAD有协同作用，且其能抑制MMPs的表达。我们采用免疫组化SP法检测MMP-7、TIMP-1、E-CAD、Syndecan-1在胃癌组织标本的表达情况，揭示它们与胃癌发生、发展的关系，评估胃癌中蛋白酶与细胞粘附的关系，以提高胃癌的早期诊治水平，也为临床应用蛋白酶抑制剂防治胃癌转移提供参考。
方法：应用免疫组化SP法方法检测36例胃癌组织及36例癌旁组织中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达水平，并分析胃癌中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达与癌细胞浸润转移等有关临床病理因素的关系。
结果：1．MMP-7在胃癌组织中的阳性表达率(58.33％)显著高于癌旁组织的阳性表达率(5.56％)(P＜0.01)。MMP-7的阳性表达与胃癌TNM分期(P＜0.01)及淋巴结转移(P＜0.05)均显著相关。
2．TIMP-1在胃癌组织中的阳性表达率(44.44％)低于癌旁组织的阳性表达率(50.00％)，但无统计学意义(P＞0.05)。TIMP-1的阳性表达与胃癌TNM分期显著相关(P＜0.05)。
3．E-CAD在胃癌组织中的阳性表达率(72.22％)显著低于癌旁组织的阳性表达率(91.67％)(P＜0.05)。E-CAD的阳性表达与胃癌分化程度显著相关(P＜0.05)。
4．Syndecan-1在胃癌组织中的阳性表达率(55.56％)显著低于癌旁组织的阳性表达率(86.11％)(P＜0.01)。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著相关(P＜0.05)。
5．胃癌中E-CAD与Syndecan-1表达强度间存在正相关(P＜0.05)，MMP-7与TIMP-1、MMP-7与E-CAD、MMP-7与Syndecan-1的表达强度之间无统计学相关(P＞0.05)。
结论：1．MMP-7在胃癌组织中的表达明显高于癌旁组织，E-CAD、Syndecan-1在胃癌组织中的表达明显低于癌旁组织，它们与胃癌的发生发展密切相关。
2．MMP-7在胃癌中的高表达与胃癌TNM分期及淋巴结转移密切相关。TIMP-1的阳性表达与胃癌TNM分期显著负相关。E-CAD的阳性表达与胃癌分化程度显著正相关。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著负相关。
3．在胃癌组织中，E-CAD与Syndecan-1的表达密切相关，提示二者之间存在某种调控关系，二者协同参与了胃癌的浸润、转移过程。
4．联合检测MMP-7、TIMP-1、E-CAD、Syndecan-1在胃癌中的表达，有助于进一步了解胃癌浸润转移的机制，预测胃癌的转移，判断其预后和选择治疗方案。
Objective Adhesion and degradation are the two committed steps of cancer cells' infiltration andmetastasis. Matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-1(TIMP-1) are relevant to the degradation of extracellular matrix (ECM). Eptithelial cadherin(E-CAD) and Syndecan-1 (CD138) mediate the adhesion of cell-ceU or cell-matrix. It is foundthat MMP-7 can destroy the junction of cells by degradating E-CAD. And there is a synergisticeffect between the expressions of Syndecan-1 and E-CAD. Besides, Syndecan-1 can alsosuppress the expression of MMPs. We detect the expressions of MMP-7, TIMP-1, E-CAD andSyndecan-1 in 36 gastric carcinomas by immunohistochemistry for studying the relationshipbetween expressions of MMP-7, TIMP-1, E-CAD, Syndecan-1 and the invasion, metastasis ingastric carcinoma. It also can evaluate the relationship between MMPs and cell adhesion ingastric carcinoma and improve the diagnosis and treatment of gastric carcinoma. Even it canprovide information for clinical application of TIMPs in the prevention and cure of gastriccarcinoma.
Methods Streptvidin-peroxidase immunohistochemistry technique (SP) was used to detect theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in 36 gastric carcinoma specimens and36 gastric mucosa membrane beside carcinoma specimens. The relationship between theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in gastric carcinoma and invasion,metastasis, clinicopathological features of gastric carcinoma was analyzed statistically.
Results 1. The positive expression rate of MMP-7 in gastric carcinoma and mucosa membranebeside carcinoma were 58.33%, 5.56% respectively. The positive expression rate of MMP-7 ingastric carcinoma was higher than that in gastric mucosa membrane beside carcinoma (P＜0.01).The positive expression of MMP-7 was significantly correlated with TNM staging (P＜0.01) andlymph node metastasis (P＜0.05), but uncorrelated to age, sex, tumor size, intravascularinvolvement, lymphatic vessel invasion, infiltration depth, and differentiation (P＞0.05). 2. Thepositive expression rate of TIMP-1 in gastric carcinoma and mucosa membrane beside carcinomawere 44.44%, 50.00% respectively. The positive expression rate of TIMP-1 in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma, but it was not significantstatistically (P＞0.05). The positive expression of TIMP-1 was significantly correlated with TNM staging (P＜0.01), but uncorrelated to age, sex, tumor size, intravascular involvement, lymphaticvessel invasion, infiltration depth, lymph node metastasis and differentiation (P＞0.05). 3. Thepositive expression rate of E-CAD in gastric carcinoma and mucosa membrane beside carcinomawere 72.22%, 91.67% respectively. The positive expression rate of E-CAD in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma (P＜0.05). The positiveexpression of E-CAD was significantly correlated with differentiation (P＜0.05), but uncorrelatedto age, sex, tumor size, intravascular involvement, lymphatic vessel invasion, infiltration depth,lymph node metastasis and TNM staging (P＞0.05). 4. The positive expression rate of Syndecan-1in gastric carcinoma and mucosa membrane beside carcinoma were 55.56%, 86.11% respectively.The positive expression rate of Syndecan-1 in gastric carcinoma was lower than that in gastricmucosa membrane beside carcinoma (P＜0.01). The positive expression of Syndecan-1 wassignificantly correlated with lymph node metastasis and infiltration depth (P＜0.05), butuncorrelated to age, sex, tumor size, intravascular involvement, lymphatic vessel invasion,differentiation and TNM staging (P＞0.05). 5.18 in 36 cases of gastric carcinoma were positivelyexpressed both E-CAD and Syndecan-1 and 8 in 36 cases were negatively expressed bothE-CAD and Syndecan-1. It indicated strong relationship between the expression of E-CAD andSyndecan-1 (P＜0.05). But the relationships of MMP-7/TIMP-1, MMP-7/E-CAD andMMP-7/Syndecan-1 were not significant statistically (P＞0.05).
Conclusion 1. The positive expression rate of MMP-7 in gastric carcinoma was higher thanthat in gastric mucosa membrane beside carcinoma. The positive expression rates of E-CAD andSyndecan-1 in gastric carcinoma were lower than that in gastric mucosa membrane besidecarcinoma. 2. The positive expression of MMP-7 was significantly correlated with TNM stagingand lymph node metastasis. The positive expression of TIMP-1 was significantly correlated withTNM staging. The positive expression of E-CAD was significantly correlated with differentiation.The positive expression of Syndecan-1 was significantly correlated with lymph node metastasisand infiltration depth. 3. The correlative expression between E-CAD and Syndecan-1 in gastriccarcinoma indicates that both of them play an important role in infiltration and metastasis ofgastric carcinoma cooperatively. 4. Combinative detection of MMP-7, TIMP-1, E-CAD andSyndecan-1 expressions in gastric carcinoma may be valued to recognize the mechanism oftumor invasion and metastasis, to evaluate the clinical progress of gastric carcinoma and to provide scientific basis for anti-angiogenesis in treatment of gastric carcinoma.
方法：应用免疫组化SP法方法检测36例胃癌组织及36例癌旁组织中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达水平，并分析胃癌中MMP-7、TIMP-1、E-CAD、Syndecan-1的表达与癌细胞浸润转移等有关临床病理因素的关系。
结果：1．MMP-7在胃癌组织中的阳性表达率(58.33％)显著高于癌旁组织的阳性表达率(5.56％)(P＜0.01)。MMP-7的阳性表达与胃癌TNM分期(P＜0.01)及淋巴结转移(P＜0.05)均显著相关。
2．TIMP-1在胃癌组织中的阳性表达率(44.44％)低于癌旁组织的阳性表达率(50.00％)，但无统计学意义(P＞0.05)。TIMP-1的阳性表达与胃癌TNM分期显著相关(P＜0.05)。
3．E-CAD在胃癌组织中的阳性表达率(72.22％)显著低于癌旁组织的阳性表达率(91.67％)(P＜0.05)。E-CAD的阳性表达与胃癌分化程度显著相关(P＜0.05)。
4．Syndecan-1在胃癌组织中的阳性表达率(55.56％)显著低于癌旁组织的阳性表达率(86.11％)(P＜0.01)。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著相关(P＜0.05)。
5．胃癌中E-CAD与Syndecan-1表达强度间存在正相关(P＜0.05)，MMP-7与TIMP-1、MMP-7与E-CAD、MMP-7与Syndecan-1的表达强度之间无统计学相关(P＞0.05)。
结论：1．MMP-7在胃癌组织中的表达明显高于癌旁组织，E-CAD、Syndecan-1在胃癌组织中的表达明显低于癌旁组织，它们与胃癌的发生发展密切相关。
2．MMP-7在胃癌中的高表达与胃癌TNM分期及淋巴结转移密切相关。TIMP-1的阳性表达与胃癌TNM分期显著负相关。E-CAD的阳性表达与胃癌分化程度显著正相关。Syndecan-1的阳性表达与胃癌淋巴结转移及浸润深度显著负相关。
3．在胃癌组织中，E-CAD与Syndecan-1的表达密切相关，提示二者之间存在某种调控关系，二者协同参与了胃癌的浸润、转移过程。
4．联合检测MMP-7、TIMP-1、E-CAD、Syndecan-1在胃癌中的表达，有助于进一步了解胃癌浸润转移的机制，预测胃癌的转移，判断其预后和选择治疗方案。
Objective Adhesion and degradation are the two committed steps of cancer cells' infiltration andmetastasis. Matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-1(TIMP-1) are relevant to the degradation of extracellular matrix (ECM). Eptithelial cadherin(E-CAD) and Syndecan-1 (CD138) mediate the adhesion of cell-ceU or cell-matrix. It is foundthat MMP-7 can destroy the junction of cells by degradating E-CAD. And there is a synergisticeffect between the expressions of Syndecan-1 and E-CAD. Besides, Syndecan-1 can alsosuppress the expression of MMPs. We detect the expressions of MMP-7, TIMP-1, E-CAD andSyndecan-1 in 36 gastric carcinomas by immunohistochemistry for studying the relationshipbetween expressions of MMP-7, TIMP-1, E-CAD, Syndecan-1 and the invasion, metastasis ingastric carcinoma. It also can evaluate the relationship between MMPs and cell adhesion ingastric carcinoma and improve the diagnosis and treatment of gastric carcinoma. Even it canprovide information for clinical application of TIMPs in the prevention and cure of gastriccarcinoma.
Methods Streptvidin-peroxidase immunohistochemistry technique (SP) was used to detect theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in 36 gastric carcinoma specimens and36 gastric mucosa membrane beside carcinoma specimens. The relationship between theexpressions of MMP-7, TIMP-1, E-CAD and Syndecan-1 in gastric carcinoma and invasion,metastasis, clinicopathological features of gastric carcinoma was analyzed statistically.
Results 1. The positive expression rate of MMP-7 in gastric carcinoma and mucosa membranebeside carcinoma were 58.33%, 5.56% respectively. The positive expression rate of MMP-7 ingastric carcinoma was higher than that in gastric mucosa membrane beside carcinoma (P＜0.01).The positive expression of MMP-7 was significantly correlated with TNM staging (P＜0.01) andlymph node metastasis (P＜0.05), but uncorrelated to age, sex, tumor size, intravascularinvolvement, lymphatic vessel invasion, infiltration depth, and differentiation (P＞0.05). 2. Thepositive expression rate of TIMP-1 in gastric carcinoma and mucosa membrane beside carcinomawere 44.44%, 50.00% respectively. The positive expression rate of TIMP-1 in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma, but it was not significantstatistically (P＞0.05). The positive expression of TIMP-1 was significantly correlated with TNM staging (P＜0.01), but uncorrelated to age, sex, tumor size, intravascular involvement, lymphaticvessel invasion, infiltration depth, lymph node metastasis and differentiation (P＞0.05). 3. Thepositive expression rate of E-CAD in gastric carcinoma and mucosa membrane beside carcinomawere 72.22%, 91.67% respectively. The positive expression rate of E-CAD in gastric carcinomawas lower than that in gastric mucosa membrane beside carcinoma (P＜0.05). The positiveexpression of E-CAD was significantly correlated with differentiation (P＜0.05), but uncorrelatedto age, sex, tumor size, intravascular involvement, lymphatic vessel invasion, infiltration depth,lymph node metastasis and TNM staging (P＞0.05). 4. The positive expression rate of Syndecan-1in gastric carcinoma and mucosa membrane beside carcinoma were 55.56%, 86.11% respectively.The positive expression rate of Syndecan-1 in gastric carcinoma was lower than that in gastricmucosa membrane beside carcinoma (P＜0.01). The positive expression of Syndecan-1 wassignificantly correlated with lymph node metastasis and infiltration depth (P＜0.05), butuncorrelated to age, sex, tumor size, intravascular involvement, lymphatic vessel invasion,differentiation and TNM staging (P＞0.05). 5.18 in 36 cases of gastric carcinoma were positivelyexpressed both E-CAD and Syndecan-1 and 8 in 36 cases were negatively expressed bothE-CAD and Syndecan-1. It indicated strong relationship between the expression of E-CAD andSyndecan-1 (P＜0.05). But the relationships of MMP-7/TIMP-1, MMP-7/E-CAD andMMP-7/Syndecan-1 were not significant statistically (P＞0.05).
Conclusion 1. The positive expression rate of MMP-7 in gastric carcinoma was higher thanthat in gastric mucosa membrane beside carcinoma. The positive expression rates of E-CAD andSyndecan-1 in gastric carcinoma were lower than that in gastric mucosa membrane besidecarcinoma. 2. The positive expression of MMP-7 was significantly correlated with TNM stagingand lymph node metastasis. The positive expression of TIMP-1 was significantly correlated withTNM staging. The positive expression of E-CAD was significantly correlated with differentiation.The positive expression of Syndecan-1 was significantly correlated with lymph node metastasisand infiltration depth. 3. The correlative expression between E-CAD and Syndecan-1 in gastriccarcinoma indicates that both of them play an important role in infiltration and metastasis ofgastric carcinoma cooperatively. 4. Combinative detection of MMP-7, TIMP-1, E-CAD andSyndecan-1 expressions in gastric carcinoma may be valued to recognize the mechanism oftumor invasion and metastasis, to evaluate the clinical progress of gastric carcinoma and to provide scientific basis for anti-angiogenesis in treatment of gastric carcinoma.
引文
[1] 袁发焕．细胞外基质、基质金属蛋白酶及其抑制因子的研究进展(J)．国外医学·临床生物化学与检验学分册，2000，21：62-65．
[2] Honda M, Mori M, Ueo H, et al. Matrix metalloproteinase-7 expression in gastric carcinoma [J]. Gut, 1996,39:444-448.
[3] 万远廉，潘义生，刘玉林，等．RT-PCR方法诊断大肠癌淋巴结微转移[J]．中国实用外科杂志，2000，20(1)：47-48．
[4] Parsons SL, Watson SA, Brown PD, et al. Matrix metalloproteinases[J]. Br J Stag, 1997,84(2): 160-166.
[5] Liu XP, Oga A, Suehiro Y, et al. Inverse relationship between matrilysin expression and proliferative activity of cells in advanced gastric carcinoma[J]. Hum Pathol, 2002, 33:741-747.
[6] Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo[J]. Cancer Lett, 2001, 173:175-182.
[7] Davies G, Jiang WG, Mason MD, et al. Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell-cell dissociation and in vitro invasionl[J]. Clin Cancer Res, 2001, 7:3289-3297.
[8] Mc Donnell S., Coffey RJ, Navre M, et al. Expression and localization of the matrix metalloproteinase Pump in human coloreetal and gastric carcinomas[J]. Mol Carcinog,1991,4: 527-533.
[9] Mizumoto H, Saito T, Ashihara K, et al. Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometfial carcinoma cells[J]. Int J Cancer, 2002,100(4):401-406.
[10] Sun JM, Zheng HC, Yang XF, Xin Y, Zhang YC. Relationship between expression of matrix metalloproteinase-7 and elinieopathobiologieal behaviors of gastric cancer[J]. Shijie Huaren Xiaohua Zhazi, 2003; 11:1310-1313.
[11] 杜月光，陈慰浙．基质金属蛋白酶在胃肠癌中的表达及其抑制剂的研究进展[J]．中国癌症杂志，2002，12：81-84．
[12] Mori M, Barnard GF, Mimori K, et al. Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas[J]. Cancer, 1995, 75(6 Suppl): 1516.
[13] Curran S, Murray GI. Matrix metalloproteinases in tumor invasion and metastasis[J]. J Pathol, 1999, 189(3):300-308.
[14] Honda M, Mori M, Ueo H, et al. Matrix metalloproteinase-7 expression in gastric carcinoma [J]. Gut, 1996,39(3):444-448.
[15] Senota A, Itoh F, Yamamoto H, et al. Relation of matfilysin messenger RNA expression with invasive activity in human gastric cancer[J]. Clin Exp Metastasis, 1998,16(4):313-321.
[16] Yamashits K, Azumano I, Mai M, et al. Expression and tissue localization of matrix metalloproteinase7(matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis[J]. Int J Cancer, 1998,79(2): 187-194.
[17] Tao HQ, Zou SC, Wang RN, Lin YZ. Relationship between gastric carcinogenesis and angiogenesis[J]. Shijie Huaren Xiaohua Zhazi, 2003; 11:43-46.
[18] Kabashima A, Maehara Y, Kakeji T, et al. Clinicopathologicol features and overexpression of matrix metalloproteinase in intramucosal gastric carcinoma with lymph node metastasis[J]. Clin Cancer Res, 2000, 6(9):3581-3584.
[19] Liotta LA, Steeg PA, Stevenson WG. Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation [J]. Cell, 1991, 64:327-336.
[20] Denhardt DT, Feng B, Edwards DR, et al. Tissue inhibitor of metalloproteinases(TIMP, aka EPA):structure, control of expression and biological functions[J]. Pharmac Ther, 1993, 59:329-341.
[21] Schultz RM, Silberman S, Persky Bet al. Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells [J]. Cancer Res, 1988, 48(19):5539-5545.
[22] 曾仲综述，韩本立审阅．基质金属蛋白酶组织抑制剂的生物学功能[J]．国外医学，分子生物学分册，2000，22(2)：84-87．
[23] Kruger A, Sanchez-Sweatman OH, Martin DC, et al. Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line[J]. Oncogene, 1998, 16(18):2419-2423.
[24] Watanabe M, Takahashi Y, Ohta T, et al. Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase -1 gene in nude mice. Cancer, 1996, 77(8): 1676-1680.
[25] Murray GI, Duncan ME, Arbuckle E, et al. Matrix metallo-proteinases and their inhibitiors in gastric cancer[J]. Gut, 1998, 43(6): 791-797.
[26] 李莉，张声，林化，等．基质金属蛋白酶和组织金属蛋白酶抑制剂表达失衡与胃癌浸润转移关系[J]．癌症，2002，21(3)：305-310．
[27] Mimori K, Mori M, Shiraishi T, et al. Clinical signification of tissue inhibitor of metalloproteinase expression in gastric carcinoma[J]. Br J Cancer, 1997, 76:531-536.
[28] Chesler L, Golde DW, Bersch N, et al. Metalloproteinase inhibition and erythroid potentiation are independent activities of tissue inhibitor of metalloproteinase- 1 [J]. Blood, 1995, 86:4506-4515.
[29] Hayakawa T, Yamashita K, Tanzawa K, et al. Growth-promoting activity of tissue inhibitor of metaloproteinase-1(TIMP-1) for a wide range of cells[J]. A possible new growth factor in serum. FEBS Lett, 1992, 298(1):29-32.
[30] Yoshikawa T, Tsuburaya A, Kobayashi O, et al. Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in patients with gastric carcinoma[J]. Cancer, 2001, 91(9):1739-1744.
[31] Yoshikawa T, Saitoh M, Tsuburaya A, et al. Tissue inhibitor of matrix metalloproteinase-1 in the plasma of patients with gastric carcinoma[J]. Cancer, 1999,86:1929-1935.
[32] Shiozaki H, Oka H, Inoue M, et al. E-cadherin mediated adhesion system in cancer cells[J]. Cancer, 1996, 77: 1605-1613.
[33] Tamura S. The E-cadherin-mediated cell-cell adhesion system in human cancers[J]. Br J Stag, 1997, 84(7):899-900.
[34] Shiozaki H, Tahara H, Oka H, et al. Expression of immunoreactive E-Cadherin molecules in human cancers[J].Am J Pathol, 1991, 139; 17-23.
[35] Behrens J, Marcel MM, Van Roy FM, et al. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of Uvomorulin-mediated cell-cell adhesion[J]. J Cell Biol, 1989, 108:2435-244.
[36] Kintner C. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain[J].Cell, 1992, 69:225-236.
[37] Jawhari A, Jordan S. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinorma: relationship with patient survival[J]. Gastroenterology, 1997, 112:46-54.
[38] Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3):184-189.
[39] Shino Y, Watanabe A, Yamada Y, et al. Clinicopathologic evalution of immunohistochemical E-cadherin expression in human gastric carcinomas [J]. Cancer, 1995, 76(11):2193-2201.
[40] 周永宁，徐采朴，彭贵勇，等．E-钙粘蛋白-连接素复合体表达与胃癌临床病理学及生存期的关系[J]．中华消化杂志，2003，23：150-153．
[41] Hugh TJ, Dillon SA, Taylor Ba, et al. Cadherin-catenin expression in primary colorectal cancer: a survival analysis[J]. Br J Cancer, 1999, 80:1046-1051.
[42] Vessey CJ, Wilding J, Folarin LY, et al. Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinomas[J]. J Pathol, 1995, 176:151-155.
[43] Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC-/-colon cancer[J]. Science, 1997, 275:1784-1787.
[44] Shimoyama Y, Hirohashi S. Expression of and P-cadherin in gastric carcinomas[J]. Cancer Res, 1991,51 (8):2185-2192.
[45] Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3):184-189.
[46] Mayer B, Johnson JP, Leitl F, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration[J]. Cancer Res, 1993, 53:1690-1695.
[47] Shino Y, Watanabe A, Yamada Y, et al. Clinicopathologic evalution of immunohistochemical E-cadherin expression in human gastric carciomaa[J]. Cancer, 1995, 76(11):2193-2201.
[48] Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinorma: relationship with patient survival[J]. Gastroenterology, 1997, 112:46-54.
[49] Karayiannakis AJ, Syrigos KN, Chatzigianni E, et al. E-cadherin expression as a differentiation marker in gastric cancer[J]. Hepatogastroenterol, 1998, 45:2437-2442.
[50] Machado JC, Carneiro F, Sobrinho-Simoes M. E-cadherin mutations in gastric carcinoma[J]. J Pathol, 2000, 191:466-467.
[51] Mali M, Andfolk H, Miettinen HM, et al. Suppression of tumor cell growth by syndecan-1 ectodomain[J]. J Biol Chem, 1994, 269(45):27795.
[52] Stanley MJ, Stanley MW, Sanderson RD, et al. Heparan sulfate-mediated cell aggregation: syndecan-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells[J]. Am J Clin Pathol, 1999, 112:377-383.
[53] 史伟峰．CD138分子生物学特性与肿瘤关系的研究进展[J]．国外医学 临床生物化学与检验学分册，2002，23：39-40．
[54] Rintala M, Inki P, Klemi P, et, al. Association of syndecan-1 with tumor grade and histology in primary invasive cervical carcinoma[J]. Gynecol Oncol, 1999, 75:3372-3378.
[55] Kumar S, Jacobs W, Dkaene K, et al. Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome[J]. J pathol, 1998, 186:3300-3305.
[56] Day RM, Hao X, Iiyas M, et al. Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence[J]. Virchows Arch, 1999, 434:2121-2125.
[57] Aitonen A, Kajanti M, Heikkila P, et al. Syndecan-I expression has prognostic significance in head and neck carcinoma[J]. Br J Cancer, 1999, 79:34558-34564.
[58] Mali M, Andfolk H, Miettinen HM, et al. Suppression of tumor cell growth by syndeean-1 ectodomain[J]. J Biol Chem, 1994, 269(45):27795.
[59] Oguri K, Okayama M. Can syndecan-1 become a prognostic factor in solid tumors? [J]. J Gastroenterol, 2004, 39:197-199.
[60] 陈俊强，詹文华，何裕隆，et al．胃癌淋巴结转移预测的Logistic回归分析[J]．中华胃肠外科杂志，2005，8(5)：436-439．
[61] Wiksten JP, Lundin J, Nordling S, et al. Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer[J]. Int J Cancer, 2001, 95(1): 1-6.
[62] 赵仲生，茹国庆，马杰．et，al．胃癌中Syndecan-1、CD44V6的表达及其临床意义 [J]．中华实验外科杂志，2004，21(5)：632．
[63] Nuovo GJ, MacConnell PB, Simsir A, et al. Correlation of the in Situ Detection of Polymerase Chain Reaction-amplifede Metalloproteinase in Complementay DNAs and their Inhibitors with Prognosis in Cervical Carcinoma[J]. Cancer Res, 1995, 55:267-275.
[64] Brew K, Dinakarpandian D, Nagases H. Tissue inhibitors of metalloproteinases: volution, structure and function[J]. Biochem Biophys Acta, 2000, 1477:267.
[65] 曾仲．基质金属蛋白酶组织抑制剂的生物学功能[J]．国外医学分子生物学分册，2000，22(2)：84．
[66] Huo N, Ichikawa Y, Kamiyama M, et al. MMP-7(matrilysin) accelerated growth of human umbilical vein endothelial cells[J]. Cancer Lett, 2002, 177(1):95-100.
[67] Fang J, Shing Y, Wiederschain D, et al. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor mode. Proc Natl Acad Sci USA, 2000, 97(8):3884-3889.
[68] Adachi Y, Yamamoto H, Itoh F, et al. Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers[J]. Int J Cancer, 2001, 95:290.
[69] Hashimoto K, Kihira Y, matuo Y, et al. Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase- 1 in human prostate[J]. Urology, 1998, 160(5): 1872.
[70] Bramhall SR, Neoptolems JP, Stamp GNH, et al. Imbalance of expression of matrix metalloproteinases(MMPs) and tissue inhibitors of the matrix metalloproteinases(TIMPs) in human pancreatic carcinoma[J]. J Pathol, 1997, 182:347.
[71] Kaushal GP, Xiong X, Athota AB, et al. Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9[J]. Br J Haematol, 1999, 104(2):365-373.
[72] Dhodapkar MV, Kelly T, Theus A, et al. Elevated levels of shed syndecan-1 correlate with turmour mass and decreased matrix metalloproteinase 9 activity in the serum of patients with multiple myeloma[J]. Br J Haematol, 1997, 99(2):368-371.
[73] Nelimarkka LO, Nikkad ST, Ravanti LS, et al. Collagenasel, stromelysin-1 and 92 kDa gelatinase are associated with tumor necrosis factor-alpha induced morphological change of human endothelial cells in vitro[J]. Matrix Biol, 1998, 17(4):293-304.
[74] 孙可望，邹寿椿，赵仲生，et al．Syndecan-1和MMP-1在胃癌组织中的表达及其临 床意义[J]．外科理论与实践，2003，8(1)：40-43．
[75] Day RM, Hao X, Ilyas M, et al. Changes in the expression of Syndecan-1 in the colorectal adenoma-carcinomas sequence[J]. Virchows Arch, 1999, 434: 121-125.
[76] Inki P, Joensuu H, Grenman R, et al. Association between Syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck[J]. Br J Cancer, 1994, 70:319-323.
[77] Leppa S, Vleminckx K, Van Roy F, et al. Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent[J]. J Cell Sci, 1996, 109(Pt6): 1393-1403.
[78] 赵仲生，茹国庆，马杰．Syndecan-1及E钙粘素在胃癌组织中的表达及其与胃癌预后的关系[J]．中华医学杂志，2003，83(12)：1096-1097．
[79] 刘迪群，吴成秋，石巍．et al．Syndecan-1和E-钙粘附素在胃癌中的表达及其临床价值[J]．中华消化内镜杂志，2005，22(2)：112-114．
[1] Bar-Or A, Nuttall RK, Duddy M, et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis[J]. Brain, 2003, 126:2738 -2749.
[2] Kraiem Z, Korem S. Matrix metalloproteinase and thyroid[J]. Thyroid, 2000,10(12):1061-1069.
[3] Gomez DE, Alonso DF, Yoshiji H, et al. Tissue inhibitor of metalloproteinases: structure, regulation and biology functions[J]. Eur J Cell Biol, 1997, 74 (2):111-122.
[4] 曾仲，韩本立．基质金属蛋白酶组织抑制剂的生物学功能．国外医学·分子生物学分册，2000，22(2)：84-87．
[2] Honda M, Mori M, Ueo H, et al. Matrix metalloproteinase-7 expression in gastric carcinoma [J]. Gut, 1996,39:444-448.
[3] 万远廉，潘义生，刘玉林，等．RT-PCR方法诊断大肠癌淋巴结微转移[J]．中国实用外科杂志，2000，20(1)：47-48．
[4] Parsons SL, Watson SA, Brown PD, et al. Matrix metalloproteinases[J]. Br J Stag, 1997,84(2): 160-166.
[5] Liu XP, Oga A, Suehiro Y, et al. Inverse relationship between matrilysin expression and proliferative activity of cells in advanced gastric carcinoma[J]. Hum Pathol, 2002, 33:741-747.
[6] Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo[J]. Cancer Lett, 2001, 173:175-182.
[7] Davies G, Jiang WG, Mason MD, et al. Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell-cell dissociation and in vitro invasionl[J]. Clin Cancer Res, 2001, 7:3289-3297.
[8] Mc Donnell S., Coffey RJ, Navre M, et al. Expression and localization of the matrix metalloproteinase Pump in human coloreetal and gastric carcinomas[J]. Mol Carcinog,1991,4: 527-533.
[9] Mizumoto H, Saito T, Ashihara K, et al. Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometfial carcinoma cells[J]. Int J Cancer, 2002,100(4):401-406.
[10] Sun JM, Zheng HC, Yang XF, Xin Y, Zhang YC. Relationship between expression of matrix metalloproteinase-7 and elinieopathobiologieal behaviors of gastric cancer[J]. Shijie Huaren Xiaohua Zhazi, 2003; 11:1310-1313.
[11] 杜月光，陈慰浙．基质金属蛋白酶在胃肠癌中的表达及其抑制剂的研究进展[J]．中国癌症杂志，2002，12：81-84．
[12] Mori M, Barnard GF, Mimori K, et al. Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas[J]. Cancer, 1995, 75(6 Suppl): 1516.
[13] Curran S, Murray GI. Matrix metalloproteinases in tumor invasion and metastasis[J]. J Pathol, 1999, 189(3):300-308.
[14] Honda M, Mori M, Ueo H, et al. Matrix metalloproteinase-7 expression in gastric carcinoma [J]. Gut, 1996,39(3):444-448.
[15] Senota A, Itoh F, Yamamoto H, et al. Relation of matfilysin messenger RNA expression with invasive activity in human gastric cancer[J]. Clin Exp Metastasis, 1998,16(4):313-321.
[16] Yamashits K, Azumano I, Mai M, et al. Expression and tissue localization of matrix metalloproteinase7(matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis[J]. Int J Cancer, 1998,79(2): 187-194.
[17] Tao HQ, Zou SC, Wang RN, Lin YZ. Relationship between gastric carcinogenesis and angiogenesis[J]. Shijie Huaren Xiaohua Zhazi, 2003; 11:43-46.
[18] Kabashima A, Maehara Y, Kakeji T, et al. Clinicopathologicol features and overexpression of matrix metalloproteinase in intramucosal gastric carcinoma with lymph node metastasis[J]. Clin Cancer Res, 2000, 6(9):3581-3584.
[19] Liotta LA, Steeg PA, Stevenson WG. Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation [J]. Cell, 1991, 64:327-336.
[20] Denhardt DT, Feng B, Edwards DR, et al. Tissue inhibitor of metalloproteinases(TIMP, aka EPA):structure, control of expression and biological functions[J]. Pharmac Ther, 1993, 59:329-341.
[21] Schultz RM, Silberman S, Persky Bet al. Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells [J]. Cancer Res, 1988, 48(19):5539-5545.
[22] 曾仲综述，韩本立审阅．基质金属蛋白酶组织抑制剂的生物学功能[J]．国外医学，分子生物学分册，2000，22(2)：84-87．
[23] Kruger A, Sanchez-Sweatman OH, Martin DC, et al. Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line[J]. Oncogene, 1998, 16(18):2419-2423.
[24] Watanabe M, Takahashi Y, Ohta T, et al. Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase -1 gene in nude mice. Cancer, 1996, 77(8): 1676-1680.
[25] Murray GI, Duncan ME, Arbuckle E, et al. Matrix metallo-proteinases and their inhibitiors in gastric cancer[J]. Gut, 1998, 43(6): 791-797.
[26] 李莉，张声，林化，等．基质金属蛋白酶和组织金属蛋白酶抑制剂表达失衡与胃癌浸润转移关系[J]．癌症，2002，21(3)：305-310．
[27] Mimori K, Mori M, Shiraishi T, et al. Clinical signification of tissue inhibitor of metalloproteinase expression in gastric carcinoma[J]. Br J Cancer, 1997, 76:531-536.
[28] Chesler L, Golde DW, Bersch N, et al. Metalloproteinase inhibition and erythroid potentiation are independent activities of tissue inhibitor of metalloproteinase- 1 [J]. Blood, 1995, 86:4506-4515.
[29] Hayakawa T, Yamashita K, Tanzawa K, et al. Growth-promoting activity of tissue inhibitor of metaloproteinase-1(TIMP-1) for a wide range of cells[J]. A possible new growth factor in serum. FEBS Lett, 1992, 298(1):29-32.
[30] Yoshikawa T, Tsuburaya A, Kobayashi O, et al. Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in patients with gastric carcinoma[J]. Cancer, 2001, 91(9):1739-1744.
[31] Yoshikawa T, Saitoh M, Tsuburaya A, et al. Tissue inhibitor of matrix metalloproteinase-1 in the plasma of patients with gastric carcinoma[J]. Cancer, 1999,86:1929-1935.
[32] Shiozaki H, Oka H, Inoue M, et al. E-cadherin mediated adhesion system in cancer cells[J]. Cancer, 1996, 77: 1605-1613.
[33] Tamura S. The E-cadherin-mediated cell-cell adhesion system in human cancers[J]. Br J Stag, 1997, 84(7):899-900.
[34] Shiozaki H, Tahara H, Oka H, et al. Expression of immunoreactive E-Cadherin molecules in human cancers[J].Am J Pathol, 1991, 139; 17-23.
[35] Behrens J, Marcel MM, Van Roy FM, et al. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of Uvomorulin-mediated cell-cell adhesion[J]. J Cell Biol, 1989, 108:2435-244.
[36] Kintner C. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain[J].Cell, 1992, 69:225-236.
[37] Jawhari A, Jordan S. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinorma: relationship with patient survival[J]. Gastroenterology, 1997, 112:46-54.
[38] Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3):184-189.
[39] Shino Y, Watanabe A, Yamada Y, et al. Clinicopathologic evalution of immunohistochemical E-cadherin expression in human gastric carcinomas [J]. Cancer, 1995, 76(11):2193-2201.
[40] 周永宁，徐采朴，彭贵勇，等．E-钙粘蛋白-连接素复合体表达与胃癌临床病理学及生存期的关系[J]．中华消化杂志，2003，23：150-153．
[41] Hugh TJ, Dillon SA, Taylor Ba, et al. Cadherin-catenin expression in primary colorectal cancer: a survival analysis[J]. Br J Cancer, 1999, 80:1046-1051.
[42] Vessey CJ, Wilding J, Folarin LY, et al. Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinomas[J]. J Pathol, 1995, 176:151-155.
[43] Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC-/-colon cancer[J]. Science, 1997, 275:1784-1787.
[44] Shimoyama Y, Hirohashi S. Expression of and P-cadherin in gastric carcinomas[J]. Cancer Res, 1991,51 (8):2185-2192.
[45] Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3):184-189.
[46] Mayer B, Johnson JP, Leitl F, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration[J]. Cancer Res, 1993, 53:1690-1695.
[47] Shino Y, Watanabe A, Yamada Y, et al. Clinicopathologic evalution of immunohistochemical E-cadherin expression in human gastric carciomaa[J]. Cancer, 1995, 76(11):2193-2201.
[48] Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinorma: relationship with patient survival[J]. Gastroenterology, 1997, 112:46-54.
[49] Karayiannakis AJ, Syrigos KN, Chatzigianni E, et al. E-cadherin expression as a differentiation marker in gastric cancer[J]. Hepatogastroenterol, 1998, 45:2437-2442.
[50] Machado JC, Carneiro F, Sobrinho-Simoes M. E-cadherin mutations in gastric carcinoma[J]. J Pathol, 2000, 191:466-467.
[51] Mali M, Andfolk H, Miettinen HM, et al. Suppression of tumor cell growth by syndecan-1 ectodomain[J]. J Biol Chem, 1994, 269(45):27795.
[52] Stanley MJ, Stanley MW, Sanderson RD, et al. Heparan sulfate-mediated cell aggregation: syndecan-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells[J]. Am J Clin Pathol, 1999, 112:377-383.
[53] 史伟峰．CD138分子生物学特性与肿瘤关系的研究进展[J]．国外医学 临床生物化学与检验学分册，2002，23：39-40．
[54] Rintala M, Inki P, Klemi P, et, al. Association of syndecan-1 with tumor grade and histology in primary invasive cervical carcinoma[J]. Gynecol Oncol, 1999, 75:3372-3378.
[55] Kumar S, Jacobs W, Dkaene K, et al. Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome[J]. J pathol, 1998, 186:3300-3305.
[56] Day RM, Hao X, Iiyas M, et al. Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence[J]. Virchows Arch, 1999, 434:2121-2125.
[57] Aitonen A, Kajanti M, Heikkila P, et al. Syndecan-I expression has prognostic significance in head and neck carcinoma[J]. Br J Cancer, 1999, 79:34558-34564.
[58] Mali M, Andfolk H, Miettinen HM, et al. Suppression of tumor cell growth by syndeean-1 ectodomain[J]. J Biol Chem, 1994, 269(45):27795.
[59] Oguri K, Okayama M. Can syndecan-1 become a prognostic factor in solid tumors? [J]. J Gastroenterol, 2004, 39:197-199.
[60] 陈俊强，詹文华，何裕隆，et al．胃癌淋巴结转移预测的Logistic回归分析[J]．中华胃肠外科杂志，2005，8(5)：436-439．
[61] Wiksten JP, Lundin J, Nordling S, et al. Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer[J]. Int J Cancer, 2001, 95(1): 1-6.
[62] 赵仲生，茹国庆，马杰．et，al．胃癌中Syndecan-1、CD44V6的表达及其临床意义 [J]．中华实验外科杂志，2004，21(5)：632．
[63] Nuovo GJ, MacConnell PB, Simsir A, et al. Correlation of the in Situ Detection of Polymerase Chain Reaction-amplifede Metalloproteinase in Complementay DNAs and their Inhibitors with Prognosis in Cervical Carcinoma[J]. Cancer Res, 1995, 55:267-275.
[64] Brew K, Dinakarpandian D, Nagases H. Tissue inhibitors of metalloproteinases: volution, structure and function[J]. Biochem Biophys Acta, 2000, 1477:267.
[65] 曾仲．基质金属蛋白酶组织抑制剂的生物学功能[J]．国外医学分子生物学分册，2000，22(2)：84．
[66] Huo N, Ichikawa Y, Kamiyama M, et al. MMP-7(matrilysin) accelerated growth of human umbilical vein endothelial cells[J]. Cancer Lett, 2002, 177(1):95-100.
[67] Fang J, Shing Y, Wiederschain D, et al. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor mode. Proc Natl Acad Sci USA, 2000, 97(8):3884-3889.
[68] Adachi Y, Yamamoto H, Itoh F, et al. Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers[J]. Int J Cancer, 2001, 95:290.
[69] Hashimoto K, Kihira Y, matuo Y, et al. Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase- 1 in human prostate[J]. Urology, 1998, 160(5): 1872.
[70] Bramhall SR, Neoptolems JP, Stamp GNH, et al. Imbalance of expression of matrix metalloproteinases(MMPs) and tissue inhibitors of the matrix metalloproteinases(TIMPs) in human pancreatic carcinoma[J]. J Pathol, 1997, 182:347.
[71] Kaushal GP, Xiong X, Athota AB, et al. Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9[J]. Br J Haematol, 1999, 104(2):365-373.
[72] Dhodapkar MV, Kelly T, Theus A, et al. Elevated levels of shed syndecan-1 correlate with turmour mass and decreased matrix metalloproteinase 9 activity in the serum of patients with multiple myeloma[J]. Br J Haematol, 1997, 99(2):368-371.
[73] Nelimarkka LO, Nikkad ST, Ravanti LS, et al. Collagenasel, stromelysin-1 and 92 kDa gelatinase are associated with tumor necrosis factor-alpha induced morphological change of human endothelial cells in vitro[J]. Matrix Biol, 1998, 17(4):293-304.
[74] 孙可望，邹寿椿，赵仲生，et al．Syndecan-1和MMP-1在胃癌组织中的表达及其临 床意义[J]．外科理论与实践，2003，8(1)：40-43．
[75] Day RM, Hao X, Ilyas M, et al. Changes in the expression of Syndecan-1 in the colorectal adenoma-carcinomas sequence[J]. Virchows Arch, 1999, 434: 121-125.
[76] Inki P, Joensuu H, Grenman R, et al. Association between Syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck[J]. Br J Cancer, 1994, 70:319-323.
[77] Leppa S, Vleminckx K, Van Roy F, et al. Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent[J]. J Cell Sci, 1996, 109(Pt6): 1393-1403.
[78] 赵仲生，茹国庆，马杰．Syndecan-1及E钙粘素在胃癌组织中的表达及其与胃癌预后的关系[J]．中华医学杂志，2003，83(12)：1096-1097．
[79] 刘迪群，吴成秋，石巍．et al．Syndecan-1和E-钙粘附素在胃癌中的表达及其临床价值[J]．中华消化内镜杂志，2005，22(2)：112-114．
[1] Bar-Or A, Nuttall RK, Duddy M, et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis[J]. Brain, 2003, 126:2738 -2749.
[2] Kraiem Z, Korem S. Matrix metalloproteinase and thyroid[J]. Thyroid, 2000,10(12):1061-1069.
[3] Gomez DE, Alonso DF, Yoshiji H, et al. Tissue inhibitor of metalloproteinases: structure, regulation and biology functions[J]. Eur J Cell Biol, 1997, 74 (2):111-122.
[4] 曾仲，韩本立．基质金属蛋白酶组织抑制剂的生物学功能．国外医学·分子生物学分册，2000，22(2)：84-87．