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[Cancer Research 59, 219-226, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 219-226, January 1, 1999]
© 1999 American Association for Cancer Research

Tumor Biology

CD44 Variants but not CD44s Cooperate with ß1-containing Integrins to Permit Cells to Bind to Osteopontin Independently of Arginine-glycine-aspartic Acid, thereby Stimulating Cell Motility and Chemotaxis1

Yohko U. Katagiri, Jonathan Sleeman, Hideki Fujii, Peter Herrlich, Hiroshi Hotta, Kumiko Tanaka, Shunsuke Chikuma, Hideo Yagita, Ko Okumura, Masaaki Murakami, Ikuo Saiki, Ann F. Chambers and Toshimitsu Uede2

Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Sapporo, 0600815, Japan [Y. U. K., H. H., K. T., S. C., M. M., T. U.]; Institute of Genetics, Forschungszentrum Karlsruhe, D-76021 Karlsruhe, Germany [J. S., P. H.]; Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical and Pharmaceutical University, 9300194 Toyama, Japan [H. F., I. S.]; Department of Immunology, Juntendo University School of Medicine, 1138421 Tokyo, Japan [H. Y., K. O.]; and Division of Experimental Oncology, Department of Oncology, The London Regional Cancer Centre, Ontario, N6A 4L6, Canada [A. F. C.]

The expression of osteopontin (OPN), CD44 variants, and integrins has been correlated with tumorigenesis and metastasis. Here we show that these proteins cooperate to enhance cell motility. First, we demonstrate that several different CD44 variants bind to OPN in an arginine-glycine-aspartic acid-independent manner, but that the standard form of CD44 does not. These CD44 variants bind to both the amino- and COOH-terminal portions of OPN independently of the arginine-glycine-aspartic acid sequence, suggesting that multiple domains on OPN can be bound by the CD44 variants. Antibodies directed against the integrin ß1 subunit are able to inhibit this binding. The binding of CD44 variants to OPN is significantly augmented by both anti-CD44s and anti-CD44v antibodies. This augmentation by anti-CD44 antibodies is OPN specific and, again, can be blocked by anti-ß1 antibodies. Finally, we show that OPN binding by CD44 variants/ß1-containing integrins promotes cell spreading, motility, and chemotactic behavior.




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