Integrin α2β1Recognizes Laminin-2 and Induces C-erb B2Tyrosine Phosphorylation in Metastatic Human Melanoma Cells

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Abstract
Previous studies have shown that tumor cells with metastatic propensity secrete more of the laminin α2 chain than non-metastatic tumor cells do, and that laminin-2, which contains the α2 chain, promotes cell adhesion better than laminin-1 (Jenq et al. (1994). Differentiation, 58, 29-36). The current studies were designed to determine whether a correlation exists between the expression of the laminin-2 isoform and the metastatic phenotype in melanoma cells. We found that expression of the laminin-2 isoform was upregulated in the metastatic melanoma cell lines tested. Cell attachment studies showed that metastatic melanoma cells attached more efficiently to laminin-2 substrates. Studies on integrin expression revealed that the presence of α2β1 integrin correlated with expression of the laminin-2 isoform in metastatic melanoma cells; anti-integrin α2 antibody prevented cell attachment to laminin-2 substrates. The data suggest that the α2β1 integrin is the receptor mediating cell attachment to the laminin-2 isoform. This interaction, mediated by the α2β1 integrin, stimulates secretion of the 72 kD type IV collagenase and induces a specific 185 kD protein tyrosine phosphorylation. The 185 kD tyrosine-phosphorylated protein was identified as the p185/C-erb B2 oncoprotein by immunoprecipitation. These studies suggest that upregulation of expression of the laminin-2 chain correlates with the metastatic phenotype of melanoma cells and provides evidence that the specific p185/C-erb B2 tyrosine phosphorylation may be involved in integrin-mediated signaling during tumor cell invasion and metastasis.

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