We compared integrin-mediated adhesion to extracellular matrix (ECM) components of cultured human melanocytes and 6 human melanoma cell lines with different metastatic capacities in nude mice. Cultured melanocytes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), collagen type I (COI) and type IV (COIV). Adhesion to LM and CO could be blocked by anti-alpha6 and anti-alpha2 monoclonal antibodies (MAbs) respectively. This observation is consistent with the finding that expression of LM receptor alpha6beta1 and LM/CO receptor alpha2beta1 was low on melanocytes and non- or poorly metastatic cell lines, whereas these 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 highly metastatic cell lines and immunohistochemistry showed expression of alpha6beta1 and alpha2beta1 only in xenograft lesions from highly metastatic cell lines. Furthermore, the observation that adhesion of melanocytes and non- or poorly metastatic cell lines could be stimulated with anti beta1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that alpha2beta1 and alpha6beta1 play a role in human melanoma metastasis in nude mice and demonstrate that interactions of these integrins with their ligands can be regulated at the level of surface expression and activation state of the receptor.
