Characterization of a monoclonal antibody that antagonizes the function of human endostatin.
Endostatin, a 20-kDa proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and tumor growth. The anti-angiogenic effects of endostatin include inhibition of endothelial cell migration and proliferation, and inhibition of the activity of MMP2. Structure-function analysis of endostatin that implies this contravention function buried in separate fragments of endostatin introduces new issues into the understanding of the structure-function relationship of endostatin. We developed and characterized a novel murine MAb, 4E7, to human endostatin, which antagonizes the function of endostatin. As we show here, MAb 4E7 blocks the anti-migration/adhesion effects of endostatin in vitro and the anti-angiogenesis effect of endostatin in vivo, but the inhibition effect of endostatin on endothelial cell proliferation is not affected by MAb4E7. These results suggest that the anti-migration and anti-proliferation functions of endostatin may have distinct structural foundations.
Feng
Yumei
Y
Genetic Engineering Department, Beijing Institute of Biotechnology, Beijing, P.R. China.
Feng
Yi
Y
Liao
Xiang
X
Zhu
Xudong
X
Zhou
Qixin
Q
Zeng
Zhaochun
Z
Ma
Qingjun
Q
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016510:Corneal Neovascularization / Q000139:chemically induced; D043169:Endostatins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D012972:Sodium Hydroxide / Q000633:toxicity; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D043169:Endostatins; D012972:Sodium Hydroxide