Reduction of Tumorigenicity by α3Integrin in a Rhabdomyosarcoma Cell Line

Abstract
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 (α3β1) in tumor cell behavior, we transfected α3 subunit cDNA into human rhabdomyosarcoma (RD) cells. Transi ectants expressing high levels of α3β1, on their cell surface displayed an altered morphology and decreased anchorage-dependent growth in vitro. Cells expressing α3 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 α3 cytoplasmic domain had been exchanged with that of the α4 integrin subunit. Therefore, α3 inhibitory effects in RD cells appear not to require specific signalling through the α3 cytoplasmic domain.