Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Angiogenesis Inhibitors
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Angiogenesis Modulating Agents / chemistry
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Angiogenesis Modulating Agents / pharmacology*
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Animals
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Cell Adhesion / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Endothelium, Vascular / cytology
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Ephrin-B2 / metabolism*
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Growth Inhibitors
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Humans
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Mice
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Neoplasms / blood supply
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Neoplasms, Experimental / drug therapy
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Neovascularization, Pathologic / drug therapy
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Protein Binding / drug effects
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Receptor, EphB4 / metabolism*
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Solubility
Substances
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Angiogenesis Inhibitors
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Angiogenesis Modulating Agents
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Ephrin-B2
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Growth Inhibitors
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Peptide Fragments
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Ephb4 protein, mouse
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Receptor, EphB4