Loss of adhesion to basement membrane components but not to keratinocytes in proliferating melanocytes.

ABSTRACT

We studied the adhesive characteristics of melanocytes, cultured either in the presence of the mitogen phorbol 12-myristate 13-acetate (PMA) that keeps them in a proliferative state, or in the absence of PMA allowing them to differentiate. On proliferating melanocytes, several integrins, 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 conditions, expression of integrins alpha 3 beta 1 and alpha 5 beta 1 decreased, 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 adhesion molecules. Immunoprecipitations from metabolically labeled cells confirmed the shift in integrin expression at the level of biosynthesis. 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 to basement membrane components collagen and laminin through these integrins. Integrin alpha 5 beta 1/alpha v beta 3-mediated adhesion to fibronectin, 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 expression of adhesion molecules, adhesion to components of the basement membrane is reduced in proliferating melanocytes, whereas adhesion to keratinocytes is maintained. Similar events may be involved in melanocyte proliferation and migration during wound healing and initial steps of melanocytic tumor progression.