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Anti-beta4 integrin antibodies enhance migratory and invasive abilities of human colon adenocarcinoma cells and their MMP-2 expression.

Abstract
Integrin-mediated adhesion of cells to extracellular matrix proteins has been shown to activate various intracellular signaling events. In the present study, we demonstrate that the addition of a monoclonal antibody raised against the beta4 integrin subunit in the culture medium of a clone derived from the colon adenocarcinoma cell line LoVo specifically results in stimulation of cell migration and invasion through reconstituted basement membrane matrices. Moreover, an increase in MMP-2 activity is observed. Conversely, monoclonal anti-alpha6 and anti-beta1 have no effect on MMP-2 expression. The s. c. co-injection of adenocarcinoma cells with antibodies raised against the beta4 integrin subunit to immunosuppressed newborn rats gives rise to tumors displaying altered and disorganized peri-tumoral basement membranes compared with tumors obtained when cells are injected with adenocarcinoma cells alone. Higher metastatic capacity of cells results when they are co-injected with antibodies to the beta4 integrin subunit. Our results suggest that the beta4 subunit of alpha6beta4 integrin, a laminin receptor in colon adenocarcinoma, may be responsible for the specific signals which stimulate cell motility, expression of MMP-2 and tumor invasion.
AuthorsN Daemi, N Thomasset, J C Lissitzky, J Dumortier, M F Jacquier, C Pourreyron, P Rousselle, J A Chayvialle, L Remy
JournalInternational journal of cancer (Int J Cancer) Vol. 85 Issue 6 Pg. 850-6 (Mar 15 2000) ISSN: 0020-7136 [Print] United States
PMID10709107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2000 Wiley-Liss, Inc.
Chemical References
  • Antibodies, Monoclonal
  • Antigens, CD
  • Integrin beta4
  • Laminin
  • laminin 1
  • Matrix Metalloproteinase 2
Topics
  • Adenocarcinoma (metabolism, pathology)
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal
  • Antigens, CD (immunology, metabolism)
  • Blotting, Southern
  • Cell Movement
  • Colonic Neoplasms (metabolism, pathology)
  • Humans
  • Immunohistochemistry
  • Integrin beta4
  • Laminin (metabolism)
  • Matrix Metalloproteinase 2 (metabolism)
  • Microscopy, Electron
  • Neoplasm Invasiveness
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

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