Upregulation of MMPS by soluble E-cadherin in human lung tumor cells

被引:102
作者
Nawrocki-Raby, B
Gilles, C
Polette, M
Bruynfeel, E
Laronze, JY
Bonnet, N
Foidart, JM
Mareel, M
Birembaut, P
机构
[1] CHU Maison Blanche, IFR 53, INSERM UMRS 514, Lab Pol Bouin, F-51092 Reims, France
[2] Univ Liege, Lab Tumor & Dev Biol, Liege, Belgium
[3] Ghent Univ Hosp, Dept Radiotherapy & Nucl Med, Expt Cancerol Lab, B-9000 Ghent, Belgium
[4] UFR Pharm, Chim Therapeut Lab, Reims, France
关键词
cancer progression; soluble E-cadherin; MMPs; cell invasion;
D O I
10.1002/ijc.11168
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Loss of E-cadherin/catenin mediated cell-cell adhesion and overexpression of matrix metalloproteinases (MMPs) are largely involved in tumor invasion. It has been recently shown that high levels of a soluble 80 kDa fragment of E-cadherin, resulting from a cleavage by IVIMPs, are found in serum and in urine from cancer patients. Additionally, this soluble E-cadherin (sE-CAD) promotes cell invasion into chick heart and into collagen type I gels. The aim of our study was to examine the mechanism of sE-CAD-induced cell invasion. Since MMPs play a crucial role in invasion, we looked for induction of MMPs by sE-CAD in noninvasive human lung tumor cells 16HBE. An induction of MMP-2, MMP-9 and MTI-MMP expression was observed both at the mRNA and at the protein level in the presence of sE-CAD (in conditioned medium form or in E-cadherin HAV peptide form). No induction of MMP-I, -3 and -7 or variation of the levels of their inhibitors, TIMP-I and TIMP-2, were detected. The biologic relevance of the sE-CAD-induced MMP upregulation was tested by demonstrating that sE-CAD promotes in vitro cell invasion in a modified Boyden chamber assay. These data provide new insight into mechanisms of tumor invasion by ectodomain shedding of the cell-cell adhesion molecule E-cadherin. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:790 / 795
页数:6
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