Upregulation of MMPs by soluble E-cadherin in human lung tumor cells.
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.
Nawrocki-Raby
Béatrice
B
INSERM UMRS 514, Laboratoire Pol Bouin, IFR 53, CHU Maison Blanche, Reims, France. beatrice.raby@univ-reims.fr
Gilles
Christine
C
Polette
Myriam
M
Bruyneel
Erik
E
Laronze
Jean-Yves
JY
Bonnet
Noël
N
Foidart
Jean-Michel
JM
Mareel
Marc
M
Birembaut
Philippe
P
D015820:Cadherins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015820:Cadherins; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases