Expression of the alpha 7 beta 1 laminin receptor suppresses melanoma growth and metastatic potential

The alpha 7 beta 1 integrin is a laminin-binding receptor that was original ly identified in melanoma, Here, we show that, in clonally derived mouse K1 735 melanoma variant cell lines with high (M-2) and low (C-23) metastatic p otential, elevated expression of alpha 7 correlates with reduced cell motil ity, metastasis, and tumor growth. Both cell lines showed similar beta 1 in tegrin-dependent adhesion to laminin-1 and the E8 laminin fragment. However , the highly metastatic M-2 cells rapidly migrated on laminin, whereas the nonmetastatic C-23 cells were minimally motile, Laminin-binding integrin pr ofiles showed that the M-2 cells expressed moderate amounts of alpha 1 and abundant alpha 6 but low or undetectable levels of alpha 2 and alpha 7, By contrast, C-23 cells expressed low or undetectable levels of alpha 1, alpha 2, and alpha 6 but had up-regulated levels of alpha 7, Consistent with the protein data, Northern blot analysis showed that levels of alpha 7 mRNA we re highest in the poorly metastatic variant cells, whereas alpha 6 message was not detected; in contrast, alpha 6 mRNA was elevated in the highly meta static cells, whereas alpha 7 message was not detected. Forced expression o f alpha 7 in the M-2 cells suppressed cell motility, tumor growth, and meta stasis. Collectively, these results indicate that, during melanoma progress ion, acquisition of a highly tumorigenic and metastatic melanoma phenotype is associated with loss of the alpha 7 beta 1 laminin receptor.