REEXPRESSION OF THE ALPHA(2)BETA(1) INTEGRIN ABROGATES THE MALIGNANT PHENOTYPE OF BREAST-CARCINOMA CELLS

To assess the role of altered alpha(2) beta(1) integrin expression in breast cancer, we expressed the alpha(2) beta(1) integrin de novo in a poorly differentiated mammary carcinoma that expressed no detectable alpha(2)-integrin subunit, Expression of the alpha(2) beta(1) integrin resulted in a dramatic phenotypic alteration from a fibroblastoid, spindle shaped, non-contact-inhibited, motile, and invasive cell to an epithelioid, polygonal-shaped, contact-inhibited, less motile, and less invasive cell. Although expression of the alpha(2) subunit did not alter adhesion to collagen, it profoundly altered cell spreading, Re-expression of the alpha(2) beta(1) integrin restored the ability to differentiate into gland-like structures in three-dimensional matrices and markedly reduced the in vivo tumorigenicity of the cells, These results indicate that the consequences of diminished alpha(2) beta(1)-integrin expression in the development of breast cancer and, presumably, of other epithelial malignancies are increased tumorigenicity and loss of the differentiated epithelial phenotype.