Metastatin: A hyaluronan-binding complex from cartilage that inhibits tumor growth

In this study, a hyaluronan-binding complex, which we termed Metastatin, wa s isolated from bovine cartilage by affinity chromatography and found to ha ve both antitumorigenic and antiangiogenic properties. Metastatin was able to block the formation of tumor nodules in the lungs of mice inoculated wit h B16BL6 melanoma or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into chicken embryos inhibited the growth of both B16BL6 mou se melanoma and TSU human prostate cancer cells growing on the chorioallant oic membrane. The in vivo biological effect may be attributed to the antian giogenic activity because Metastatin is able to inhibit the migration and p roliferation 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 d epends 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.