ALPHA(V) INTEGRINS MEDIATE ADHESION AND MIGRATION OF BREAST-CARCINOMACELL-LINES

Integrins with the alpha(v) subunit are involved in cell adhesion and cellular signaling. Some alpha(v) integrins have been associated with tumor progression and dissemination. The objective of this study was t o assess the contribution of alpha(v) integrins to the adhesive and mi gratory behavior of cells derived from breast carcinoma (BCA). The exp ression and function of alpha(v) integrins was characterized in three BCA cell lines which exhibit different metastatic potentials. These in clude MCF-7 cells which metastasize inefficiently, MDA-MB-231 cells, w hich have a moderate metastatic potential, and MDA-MB-435 cells, which metastasize extensively. Each cell type displays a different repertoi re of alpha(v) integrins on the cell surface, The complement of alpha( v) integrins on each cell type influences their ability to adhere and migrate. The most striking difference among these cell lines was the e xpression of the alpha(v) beta(3) integrin. The highly metastatic MDA- MB-435 cells express substantial levels of this receptor, whereas MDA- MB-231 and MCF-7 cells do not. The MDA-MB-435 cells showed a greater a bility to adhere and to migrate and this functional difference can lar gely be attributed to the expression of alpha(v) beta(3) integrin. Thi s characterization is a first step toward determining the role of alph a(v) integrins in animal models of BCA metastasis, and lends support t o the hypothesis that the alpha(v) beta(3) integrin can be a contribut ing factor in metastatic disease.