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Anti-β4 integrin antibodies enhance migratory and invasive abilities of human colon adenocarcinoma cells and their MMP-2 expression

✍ Scribed by Noucha Daemi; Nicole Thomasset; Jean-Claude Lissitzky; Jérôme Dumortier; Marie-France Jacquier; Céline Pourreyron; Patricia Rousselle; Jean-Alain Chayvialle; Lionel Remy


Book ID
101234908
Publisher
John Wiley and Sons
Year
2000
Tongue
French
Weight
300 KB
Volume
85
Category
Article
ISSN
0020-7136

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✦ Synopsis


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 ␤4 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-␣6 and anti-␤1 have no effect on MMP-2 expression. The s.c. co-injection of adenocarcinoma cells with antibodies raised against the ␤4 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 ␤4 integrin subunit. Our results suggest that the ␤4 subunit of ␣6␤4 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. Int.