Endostatin, Recombinant, Human (COL18A1)

Endostatin, an endogenous non-glycosylated inhibitor of endothelial cell proliferation and angiogenesis, is an ~181aa, 20kD 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 ~27aa 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 a5b1 and an b3, 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-egulation 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). Source: Recombinant corresponding to aa1154-1335 from human endostatin at N-terminal, fused to 8-His-tag expressed in E.coli (NP_569712). Molecular Weight: ~21.6kD Biological Activity: Measured by its ability to inhibit the FGF basic-dependent proliferation of HUVEC human umbilical vein endothelial cells. The ED50 for this effect is typically 0.4-2ug/ml. Endotoxin: <0.10 EU per 1ug of protein by the LAL method Storage and Stability: Lyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with sterile buffer or ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 6 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.