Cell Growth & Differentiation Vol. 10, 479-490, July 1999
© 1999 American Association for Cancer Research
Expression of the 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 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.
Copyright © 1999 by the American Association of Cancer Research.