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

Int J Cancer. 2000 Mar 15;85(6):850-6. doi: 10.1002/(sici)1097-0215(20000315)85:6<850::aid-ijc19>3.0.co;2-b.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Blotting, Southern
  • Cell Movement
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Integrin beta4
  • Laminin / metabolism
  • Matrix Metalloproteinase 2 / metabolism*
  • Microscopy, Electron
  • Neoplasm Invasiveness*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Integrin beta4
  • Laminin
  • laminin 1
  • Matrix Metalloproteinase 2