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Regulation of integrin‐mediated adhesion to laminin and collagen in human melanocytes and in non‐metastatic and highly metastatic human melanoma cells
Author(s) -
Danen Erik H. J.,
Van Muijen Goos N. P.,
Jansen Kees F. J.,
Ruiter Dirk J.,
Van De Wielvan Kemenade Elly,
Figdor Carl G.
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910540225
Subject(s) - integrin , fibronectin , cell culture , extracellular matrix , laminin , biology , cell adhesion , cell adhesion molecule , receptor , cancer research , melanoma , cell , microbiology and biotechnology , pathology , medicine , biochemistry , genetics
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‐α6 and anti‐α2 monoclonal antibodies (MAbs) respectively. This observation is consistent with the finding that expression of LM receptor α 6 β 1 and LM/CO receptor α 2 β 1 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 [ 35 S]‐methionine‐labeled cells demonstrated increased synthesis of α 6 , α 2 and β 1 in highly metastatic cell lines and immunohis‐tochemistry showed expression of α 6 β 1 and α 2 β 1 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 β 1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that α 2 β 1 and α 6 β 1 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.