REGULATION OF INTEGRIN-MEDIATED ADHESION TO LAMININ AND COLLAGEN IN HUMAN MELANOCYTES AND IN NONMETASTATIC AND HIGHLY METASTATIC HUMAN-MELANOMA CELLS

We compared integrin-mediated adhesion to extracellular matrix (ECM) c omponents of cultured human melanocytes and 6 human melanoma cell line s with different metastatic capacities in nude mice. Cultured melanocy tes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), co llagen type I (COI) and type IV (COIV). Adhesion to LM and CO could be blocked by anti-alpha6 and anti-alpha2 monoclonal antibodies (MAbs) r espectively. This observation is consistent with the finding that expr ession of LM receptor alpha6beta1 and LM/CO receptor alpha2beta1 was l ow on melanocytes and non- or poorly metastatic cell lines, whereas th ese integrins were strongly expressed on highly metastatic cell lines. In addition, immunoprecipitation from [S-35]-methionine-labeled cells demonstrated increased syntheSiS Of alpha6, alpha2 and beta1 in highl y metastatic cell lines and immunohistochemistry showed expression of alpha6beta1 and alpha2beta1 only in xenograft lesions from highly meta static cell lines. Furthermore, the observation that adhesion of melan ocytes and non- or poorly metastatic cell lines could be stimulated wi th anti beta1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that alpha2bet a1 and alpha6beta1 play a role in human melanoma metastasis in nude mi ce and demonstrate that interactions of these integrins with their lig ands can be regulated at the level of surface expression and activatio n state of the receptor.