EphB4的可溶性细胞外结构域（sEphB4）可拮抗EphB4-EphrinB2相互作用，调节血管生成，并抑制肿瘤生长。
The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth.
作者信息
Kertesz Nathalie, Krasnoperov Valery, Reddy Ramachandra, Leshanski Lucy, Kumar S Ram, Zozulya Sergey, Gill Parkash S
机构信息
Vasgene Therapeutics, Inc, 1929 Zonal Ave, Los Angeles, CA 90033, USA.
出版信息
Blood. 2006 Mar 15;107(6):2330-8. doi: 10.1182/blood-2005-04-1655. Epub 2005 Dec 1.
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.
摘要
受体酪氨酸激酶EphB4及其配体EphrinB2在胚胎发育过程中的血管生成中起着关键作用。EphB4胞外域的可溶性单体衍生物（sEphB4）被设计为EphB4/EphrinB2信号通路的拮抗剂。sEphB4可阻断EphB4和EphrinB2的激活；在体外抑制内皮细胞迁移、黏附和管腔形成；并在体内抑制多种生长因子（VEGF和bFGF）的血管生成作用。sEphB4还可抑制小鼠肿瘤异种移植模型中的肿瘤生长。因此，sEphB4是血管增殖性疾病和癌症的一种治疗候选药物。
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本文引用的文献
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2
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3
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