THE EXPRESSION OF INTEGRIN ALPHA-2-BETA-1 AND ATTACHMENT TO TYPE-I COLLAGEN OF MELANOMA-CELLS ARE PREFERENTIALLY INDUCED BY TUMOR PROMOTER,TPA (12-O-TETRADECANOYL PHORBOL-13-ACETATE)

The adhesion of melanoma cells to the extracellular matrix (ECM) prote in is likely to be essential in their invasive metastatic processes. T reatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent pr otein kinase C (PKC) activator, preferentially induced the expression of alpha 2 beta 1 integrin, the receptor for collagen/laminin. The num ber of cells attached to type I collagen, but not laminin, was increas ed by treatment with TPA. Prior exposure to PKC inhibitors such as H-7 (20 mu mol/l) and calphostin C(50 mu mol/l) had no effect on TPA-indu ced alpha 2 beta 1 integrin expression and cell attachment to type I c ollagen, whereas prior exposure to the calmodulin antagonist W-7(50 mu mol/l) inhibited these TPA-induced events. The augmented adhesion was also inhibited by anti-alpha 2 antibody. These data suggest that the increased attachment of melanoma cells to type I collagen appears to b e mediated by the preferential augmentation of integrin alpha 2 beta 1 , and the activation of calmodulin kinase, but not via the activation of PKC. Analysis of the expression of integrins and of cell attachment to ECMs is important in elucidating the mechanisms involved in the pr ogression and metastasis of malignant melanoma.