Reduction of tumorigenicity by alpha(3) integrin in a rhabdomyosarcoma cell line

The expression levels of integrin adhesion receptors have often been correlated with neoplastic transformation and invasiveness, To investigate more definitively the role of the integrin VLA-3 (alpha(3) beta(1)) in tumor cell behavior, we transfected alpha(3) subunit cDNA into human rhabdomyosarcoma (RD) cells. Transfectants expressing high levels of alpha(3) beta(1) on their cell surface displayed an altered morphology and decreased anchorage-dependent growth in vitro. Cells expressing alpha(3) also displayed marked reduction in anchorage-independent growth in soft agar and in their ability to form tumors when injected subcutaneously into athymic nude mice. Thus, VLA-3 can repress the transformed phenotype of rhabdomyosarcoma tumor cells. Similar changes in morphology and growth characteristics were observed in cells expressing a chimeric molecule X3C4 in which the alpha(3) cytoplasmic domain had been exchanged with that of the alpha(4) integrin subunit. Therefore, alpha(3) inhibitory effects in RD cells appear not to require specific signalling through the alpha(3) cytoplasmic domain.