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.