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

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 beta 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-alpha 6 and anti-beta 1 have no effect on MMP-2 expression. The s.c. co-injection of adenocarcinoma cells with antibodies raised against the beta 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 atone. Higher metastatic capacity of cells results when they are co-injected with antibodies to the beta 4 integrin subunit, Our results suggest that the beta 4 subunit of alpha 6 beta 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. (C) Wiley-Liss, Inc.