Endostatin

Endostatin is a 20 kDa C-terminal fragment of collagen XVIII. The exact molecular mass determined by ESI-MS was found to be 18 494 Da.Endostatin specifically inhibits. endothelial proliferation and potently inhibits angiogenesis and tumor growth. Anti-endostatin monoclonal antibody administered to nude mice transplanted with human hepatocellular carcinoma cells (JHH-1 line) that endogenously produced endostatin promoted tumor angiogenesis by inhibiting endostatin activity in the tumor and subsequently increased tumor mass by preventing cancer cells from undergoing apoptosis. The ability of endostatin to bind Zn2+ is essential for its antiangiogenic activity. The endostatin precursor collagen XVIII is expressed at high levels in human livers, the main source being hepatocytes. The generation of endostatin or endostatin-like collagen XVIII fragments is catalyzed by proteolytic enzymes, including cathepsin L and matrix metalloproteases, that cleave peptide bonds within the protease-sensitive hinge region of the C-terminal domain. The processing of collagen XVIII to endostatin may represent a local control mechanism for the regulation of angiogenesis. Circulating endostatin was detected in patients with various types of cancer as well as in healthy controls. Circulating endostatin concentrations are significantly increased in patients with systemic sclerosis. Interestingly, pericardial fluid levels of endostatin are associated with the presence (40% lower levels) or absence of collaterals in patients with CAD.