Expression of the a7b1 Laminin Receptor Suppresses Melanoma Growth and Metastatic Potential

The a7b1 integrin is a laminin-binding receptor that was originally identified in melanoma. Here, we show that, in clonally derived mouse K1735 melanoma variant cell lines with high (M-2) and low (C-23) metastatic potential, elevated expression of a7 correlates with reduced cell motility, metastasis, and tumor growth. Both cell lines showed similar b1 integrin-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 profiles showed that the M-2 cells expressed moderate amounts of a1 and abundant a6 but low or undetectable levels of a2 and a7. By contrast, C-23 cells expressed low or undetectable levels of a1, a2, and a6 but had up-regulated levels of a7. Consistent with the protein data, Northern blot analysis showed that levels of a7 mRNA were highest in the poorly metastatic variant cells, whereas a6 message was not detected; in contrast, a6 mRNA was elevated in the highly metastatic cells, whereas a7 message was not detected. Forced expression of a7 in the M-2 cells suppressed cell motility, tumor growth, and metastasis. Collectively, these results indicate that, during melanoma progression, acquisition of a highly tumorigenic and metastatic melanoma phenotype is associated with loss of the a7b1 laminin receptor.