Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines

Citation
A. Menke et al., Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines, CANCER RES, 61(8), 2001, pp. 3508-3517
Citations number
58
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
61
Issue
8
Year of publication
2001
Pages
3508 - 3517
Database
ISI
SICI code
0008-5472(20010415)61:8<3508:DOEGEB>2.0.ZU;2-G
Abstract
E-cadherin-mediated cell-cell adhesion is reduced in epithelial tumors, whi ch is thought to be a prerequisite to acquire invasive properties. We obser ved that several pancreatic carcinoma cell lines with high metastatic poten tial expressed normal levels of E-cadherin and possessed functional E-cadhe rin/catenin adhesion complexes. When the cell: lines PANG-I, BxPC-3, and Pa Tu8988s were cultured either on type I or type III collagen, E-cadherin gen e expression was repressed, and E-cadherin and catenin protein concentratio ns mere reduced In contrast, growth on fibronectin and collagen type IV had no influence, Collagen type I- or type III-dependent reduction of E-cadher in expression led to decreased cell-cell adhesion, increased proliferation, and migratory activity as cell as morphological transformation. Overexpres sion of activated c-Src in PANG-I cells mimicked collagen-induced E-cadheri n down-regulation and changed the elevated cell proliferation and migration . Conversely, treatment of cells with the Src-inhibitors PP1 or herbimycin A resulted in complete suppression of collagen type I-induced E-cadherin de crease. Our data demonstrate that specific collagens are able to promote me tastatic behavior by down-regulation of E-cadherin gene expression in a Src -kinase-dependent manner. This points toward a novel mechanism for substrat e-dependent signaling and underlines the significance of extracellular matr ix environment for tumor growth and invasiveness.