rhEndostatin, CF (50 ug)

Background: 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 (1, 2). It is produced and/or trimmed by metalloproteinases such as MMP‑2 and MMP‑9, and cathepsins S, B and L (3, 4). The N‑terminal ~27 aa of Endostatin appear to contain the majority of its activity (4, 5). This region contains three zinc binding sites that are thought to be critical for its anti‑endothelial and anti‑tumor effects, as well as multiple cleavage sites that, when used, can modify its activity (4, 5). 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 (1, 2). It is also thought to down‑regulate angiogenesis by blocking VEGF‑induced endothelial cell migration (6, 7). It alters the effect of FGF basic on adhesion and cell motility (8). Endostatin can interact with Transglutaminase 2, heparin, and integrins alpha 5 beta 1 and alpha v beta 3, all of which may be secreted by, or expressed on, endothelial cells, and can influence adhesion or migration (9, 10). Endostatin may also be involved with down‑regulation of angiogenesis after establishment of placental circulation in the pregnant uterus (11). Over‑expression in keratinocytes causes delay in healing of excisional wounds, while exogenous systemic Endostatin promotes endothelial and smooth muscle nitric oxide production and decreases blood pressure (12, 13). Since tumor growth and metastasis relies on angiogenesis to provide blood supply, Endostatin is inhibitory for a wide variety of primary and metastatic tumors (5‑8).