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Expression of the 7ß1 Laminin Receptor Suppresses Melanoma Growth and Metastatic Potential¹

Departments of Stomatology [B. L. Z., Y. Q. C., D. M. R., R. H. K.] and Anatomy [R. H. K.], University of California San Francisco, San Francisco, California 94143; and SRI International, Menlo Park, California 94025 [N. W.]

The 7ß1 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 7 correlates with reduced cell motility, metastasis, and tumor growth. Both cell lines showed similar ß1 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 1 and abundant 6 but low or undetectable levels of 2 and 7. By contrast, C-23 cells expressed low or undetectable levels of 1, 2, and 6 but had up-regulated levels of 7. Consistent with the protein data, Northern blot analysis showed that levels of 7 mRNA were highest in the poorly metastatic variant cells, whereas 6 message was not detected; in contrast, 6 mRNA was elevated in the highly metastatic cells, whereas 7 message was not detected. Forced expression of 7 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 7ß1 laminin receptor.

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