LOSS OF ADHESION TO BASEMENT-MEMBRANE COMPONENTS BUT NOT TO KERATINOCYTES IN PROLIFERATING MELANOCYTES

We studied the adhesive characteristics of melanocytes, cultured eithe r in the presence of the mitogen phorbol 12-myristate W-acetate (PMA) that keeps them in a proliferative state, or in the absence of PMA all owing them to differentiate. On proliferating melanocytes, several int egrins, ICAM-1, E-cadherin, and CD44 were expressed, in the absence of PMA, proliferation was arrested, melanin synthesis increased, and the morphology of the melanocytes became more spreaded, Under these condi tions, expression of integrins alpha 3 beta 1 and alpha 5 beta 1 decre ased, whereas expression of alpha 2 beta 1, alpha 4 beta 1, and alpha 6 beta 1 increased. No changes were observed for any of the other adhe sion molecules. Immunoprecipitations from metabolically labeled cells confirmed the shift in integrin expression at the level of biosynthesi s. The increased surface expression of alpha 2 beta 1 and alpha 6 beta 1 in the absence of PMA was accompanied by an induction of adhesion t o basement membrane components collagen and laminin through these inte grins, Integrin alpha 5 beta 1/alpha v beta 3-mediated adhesion to fib ronectin, CD44-mediated adhesion to hyaluronate, and E-cadherin/beta 1 -integrin-mediated adhesion to keratinocytes were not affected by PMA. These findings indicate that by selective modulation of the expressio n of adhesion molecules, adhesion to components of the basement membra ne is reduced in proliferating melanocytes, whereas adhesion to kerati nocytes is maintained, Similar events may be involved in melanocyte pr oliferation and migration during wound healing and initial steps of me lanocytic tumor progression.