Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion

In the current study, two specific glycosaminoglycan lyases, chondroitinase AC and chondroitinase B, were utilized to examine the roles of chondroitin sulfates and dermatan sulfate in tumor metastasis and angiogenesis. Melano ma cells (SK-MEL) or endothelial cells were treated with either medium or c hondroitinase enzyme. Chondroitinase AC inhibited melanoma invasion and pro liferation as well as endothelial proliferation and angiogenesis. Apoptosis of melanoma and endothelial cells, as measured by the activity of caspase- 3, was also increased by chondroitinase AC, but not by chondroitinase B. Ch ondroitinase B inhibited endothelial and melanoma proliferation and invasio n, but to a lesser extent than chondroitinase AC. Neither chondroitinase ha d a detectable effect on gelatinase secretion by melanoma cells. These resu lts indicate that both chondroitin and dermatan sulfates regulate many cell ular activities related to metastasis. (C) 2001 Elsevier Science B.V. All r ights reserved.