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Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: Relevance to intracellular signaling pathways

查看全文 作　　者：Elke [1]Roeb;Anja-Katrin [2]Bosserhoff;Sabine [1]Hamacher;Bettina [1]Jansen;Judith [1]Dahmen;Sandra [1]Wagner;Siegfried [1]Matern 高影响力作者 机构地区：[1]Department of Internal Medicine Ⅲ;[2]Institute of Pathology高影响力机构 出　　处：《World Journal of Gastroenterology》索引2005年第11卷第8期,共9页高影响力期刊 基　　金：Supported by grants from the Federal Ministry of Education Research of Germany, Deutsche Forschungsgemeinschaft (DFG), and Aachen University 摘　　要：AIM: To study the effect of gelatinases (especially MMP-9)on migration of tissue inhibitor of metalloproteinase (TIMP-1) overexpressing hepatoma cells.METHODS: Wild type HepG2 cells, cells stably transfected with TIMP-1 and TIMP-1 antagonist (MMP-9-H401A, a catalytically inactive matrix metalloproteinase (MMP) which still binds and neutralizes TIMP-1) were incubated in Boyden chambers either with or without Galardin (a synthetic inhibitor of MMP-1, -2, -3, -8, -9) or a specific inhibitor of gelatinases.RESULTS: Compared to wild type HepG2 cells, the cells overexpressing TIMP-1 showed 115% migration (P<0.05)and the cells overexpressing MMP-9-H401A showed 62% migration (P<0.01). Galardin reduced cell migration dose dependently in all cases. The gelatinase inhibitor reduced migration in TIMP-1 overexpressing cells predominantly.Furthermore, we examined intracellular signal transduction pathways of TIMP-1-dependent HepG2 cells. TIMP-1deactivates cell signaling pathways of MMP-2 and MMP-9involving p38 mitogen-activated protein kinase. Specific blockade of the ERK pathway suppresses gelatinase expression either in the presence or absence of TIMP-1.CONCLUSION: Overexpressing functional TIMP-1-enhanced migration of HepG2-TIMP-1 cells depends on enhanced MMP-activity, especially MMP-9. 关 键 词：肝细胞瘤 白明胶酶 肿瘤细胞 细胞内信号 信号路径
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