Endostatin

Endostatin, an endogenous non-glycosylated inhibitor of endothelial cell proliferation and angiogenesis, is an approximately 181 amino acid (aa), 20 kDa proteolytic fragment of the C-terminal non collagenous domain of type XVIII collagen. It is produced and/or trimmed by metalloproteinases such as MMP2 and MMP9, and cathepsins S, B and L. The Nterminal ~27 aa of Endostatin appear to contain the majority of its activity. This region contains three zinc binding sites that are thought to be critical for its anti-endothelial and ant-itumor effects, as well as multiple cleavage sites that, when used, can modify its activity. Human Endostatin shares 84-87% aa sequence identity with mouse, rat, bovine and equine Endostatin. Endostatin inhibits endothelial cell growth by inducing cell cycle arrest in G1 phase and initiating apoptosis. It is also thought to downregulate angiogenesis by blocking VEGF-induced endothelial cell migration. It alters the effect of FGF basic on adhesion and cell motility. Endostatin can interact with Transglutaminase 2, heparin, and integrins α5β1 and αv β3, all of which may be secreted by, or expressed on, endothelial cells, and can influence adhesion or migration.