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[Cancer Research 61, 1022-1028, February 1, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

Metastatin: A Hyaluronan-binding Complex from Cartilage That Inhibits Tumor Growth1

Ningfei Liu2, Randall K. Lapcevich2, Charles B. Underhill, Zeqiu Han, Feng Gao, Glenn Swartz, Stacy M. Plum, Lurong Zhang2 and Shawn J. Green2, 3

Department of Oncology, Georgetown University Medical Center, Washington, D.C. 20007 [N. L., C. B. U., Z. H., F. G., L. Z.], and EntreMed, Inc., Rockville, Maryland 20902 [R. K. L., G. S., S. M. P., S. J. G.]

In this study, a hyaluronan-binding complex, which we termed Metastatin, was isolated from bovine cartilage by affinity chromatography and found to have both antitumorigenic and antiangiogenic properties. Metastatin was able to block the formation of tumor nodules in the lungs of mice inoculated with B16BL6 melanoma or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into chicken embryos inhibited the growth of both B16BL6 mouse melanoma and TSU human prostate cancer cells growing on the chorioallantoic membrane. The in vivo biological effect may be attributed to the antiangiogenic activity because Metastatin is able to inhibit the migration and proliferation of cultured endothelial cells as well as vascular endothelial growth factor-induced angiogenesis on the chorioallantoic membrane. In each case, the effect could be blocked by either heat denaturing the Metastatin or premixing it with hyaluronan, suggesting that its activity critically depends on its ability to bind hyaluronan on the target cells. Collectively, these results suggest that Metastatin is an effective antitumor agent that exhibits antiangiogenic activity.




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Copyright © 2001 by the American Association for Cancer Research.