Restoration of alpha v beta 5 integrin expression in neoplastic keratinocytes results in increased capacity for terminal differentiation and suppression of anchorage-independent growth.

Loss of expression of specific integrins is a feature of poorly differentiated oral squamous cell carcinomas (SCCs) and cell lines derived from them. In order to test whether there is a direct link between loss of integrins and abnormal keratinocyte growth and differentiation, we 'repaired' an SCC line, H357, by transfection of its missing integrin subunit, alpha v. We analysed seven independent alpha v-expressing clones and compared them with four empty vector controls and with the parental cell line. alpha v was expressed on the cell surface as a functional alpha v beta 5 heterodimer. The parental cells expressed beta 5 mRNA and introduction of alpha v had no effect on beta 5 mRNA levels nor on cell surface levels of any other integrins examined. Introduction of alpha v had no consistent effect on the growth rate of cells on tissue culture plastic. However, anchorage-independent growth was strongly suppressed and the alpha v-transfectants showed an increased capacity for terminal differentiation, as assayed by expression of involucrin. These results are consistent with the known role of integrins in regulating keratinocyte terminal differentiation and suggest that integrin loss may be directly responsible for the abnormal behaviour of keratinocytes in a subset of oral SCCs.