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Cell Growth & Differentiation Vol. 10, 479-490, July 1999
© 1999 American Association for Cancer Research

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

Barry L. Ziober2, Yao Qi Chen, Daniel M. Ramos, Nahid Waleh and Randall H. Kramer3

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 {alpha}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 {alpha}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 {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 were highest in the poorly metastatic variant cells, whereas {alpha}6 message was not detected; in contrast, {alpha}6 mRNA was elevated in the highly metastatic cells, whereas {alpha}7 message was not detected. Forced expression of {alpha}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 {alpha}7ß1 laminin receptor.




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Copyright © 1999 by the American Association of Cancer Research.