ROLE OF ALPHA(5)BETA(1) INTEGRIN IN DETERMINING MALIGNANT PROPERTIES OF COLON-CARCINOMA CELLS

We characterized the expression of alpha(5) beta(1) integrin in two di stinct phenotypes of colon carcinoma cell lines, Highly invasive colon cell lines (designated Group I cell lines) expressed higher levels of integrin alpha(5) beta(1) mRNA and protein than did poorly invasive c olon cell lines (designated Group III cell lines), The relatively high expression of integrin alpha(5) beta(1) in Group I cell lines resulte d in strong enhancement of cell adhesion to fibronectin (FN) tissue cu lture plates, whereas Group III cell lines showed little or no enhance ment of cell adhesion by coating, There was no significant difference between Group I and Group III cell lines with respect to cell adhesion to laminin and collagen IV, Cell adhesion to FN in Group I cells was mainly mediated by integrin alpha(5) beta(1) because a monoclonal anti -alpha(5) subunit antibody could block cell adhesion to FN, whereas an ti-alpha(2) and anti-alpha(3) antibodies had no effect on cell adhesio n to FN. The divergence of alpha(5) beta(1) expression in these two di stinct colon carcinoma phenotypes suggested that high expression of al pha(5) beta(1) might contribute to malignant progression in this model system, To test this hypothesis, GEO cells, a Group III cell line tha t did not express alpha(5) integrin, were transfected with the alpha(5 ) subunit, Stable transfection of alpha(5) sense cDNA into a typical G EO-limiting dilution clone led to the expression of alpha(5) subunit m RNA and cell surface alpha(5) beta(1) protein, The alpha(5) sense tran sfectants showed enhanced attachment to PH-coated plates and were more tumorigenic when the cells were injected into athymic nude mice, Thes e results indicate that inappropriately high alpha(5) beta(1) integrin expression contributes to malignant progression in colon carcinoma.