THE INTEGRIN ALPHA-6-BETA-4 AND THE BIOLOGY OF CARCINOMA

The integrin family of adhesion receptors plays a major role in epithe lial organization and function. Moreover, the altered expression and f unction of specific integrins most likely contributes significantly to carcinoma progression. The integrin alpha 6 beta 4, the focus of this review, is a receptor for several members of the laminin family and i s preferentially expressed at the basal surface of most epithelia, whe re it contributes to basement membrane interactions. Mounting evidence suggests that the alpha 6 beta 4 integrin plays a key role in carcino ma cell biology. Several histopathological studies have established a correlation between alpha 6 beta 4 integrin expression and tumor progr ession The importance of alpha 6 beta 4 expression in tumors is unders cored by the findings that invading fronts of several carcinomas are e nriched in the expression of alpha 6 beta 4 integrin ligands, such as laminin-1 and laminin-5. The participation of the alpha 6 beta 4 integ rin in invasion is supported further by in vitro functional studies us ing carcinoma cells that have been transfected with the beta 4 cDNA. T he mechanisms by which alpha 6 beta 4 contributes to tumor progression are probably related to its mechanical and signaling properties and a re currently under intense study.