The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth.
The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play a crucial role in vascular development during embryogenesis. The soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling. sEphB4 blocks activation of EphB4 and EphrinB2; suppresses endothelial cell migration, adhesion, and tube formation in vitro; and inhibits the angiogenic effects of various growth factors (VEGF and bFGF) in vivo. sEphB4 also inhibits tumor growth in murine tumor xenograft models. sEphB4 is thus a therapeutic candidate for vascular proliferative diseases and cancer.
Kertesz
Nathalie
N
Vasgene Therapeutics, Inc, 1929 Zonal Ave, Los Angeles, CA 90033, USA.
Krasnoperov
Valery
V
Reddy
Ramachandra
R
Leshanski
Lucy
L
Kumar
S Ram
SR
Zozulya
Sergey
S
Gill
Parkash S
PS
D020533:Angiogenesis Inhibitors; D043924:Angiogenesis Modulating Agents / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D036388:Ephrin-B2 / Q000378:metabolism*; D006131:Growth Inhibitors; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D036224:Receptor, EphB4 / Q000378:metabolism*; D012995:Solubility
D020533:Angiogenesis Inhibitors; D043924:Angiogenesis Modulating Agents; D036388:Ephrin-B2; D006131:Growth Inhibitors; D010446:Peptide Fragments; C086681:Ephb4 protein, mouse; D036224:Receptor, EphB4