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

Abstract : 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 MMPs, 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 MT1-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-1, -3 and -7 or variation of the levels of their inhibitors, TIMP-1 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.
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Contributor : Philippe Birembaut <>
Submitted on : Friday, May 25, 2007 - 10:19:54 AM
Last modification on : Thursday, May 3, 2018 - 3:58:02 PM




Béatrice Nawrocki-Raby, Christine Gilles, Myriam Polette, Erik Bruyneel, Jean-Yves Laronze, et al.. Upregulation of MMPs by soluble E-cadherin in human lung tumor cells.. International Journal of Cancer, Wiley, 2003, 105 (6), pp.790-5. ⟨10.1002/ijc.11168⟩. ⟨inserm-00149299⟩



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