Antiangiogenic Therapeutic Potential of Peptides Derived from the Molecular Motor KIF13B that Transports VEGFR2 to Plasmalemma in Endothelial Cells

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• 作者：Kaori H. Yamada^&lowast ; ; ^&dagger ; ; ^{horiguch@uic.edu} ; Hojin Kang^&lowast ; ; ^&dagger ; ; Asrar B. Malik^&lowast ; ; ^&dagger ; ; ^{abmalik@uic.edu}
• 刊名：The American Journal of Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：187
• 期：1
• 页码：214-224
• 全文大小：3418 K
• 卷排序：187

文摘

Vascular endothelial growth factor receptor 2 (VEGFR2) localized on the surface of endothelial cells (ECs) is a key determinant of the magnitude and duration of angiogenesis induced by vascular endothelial growth factor (VEGF). The kinesin family plus-end motor KIF13B transports VEGFR2 to the EC surface, and as such, specific inhibition of polarized VEGFR2 trafficking prevents angiogenesis. We designed a series of bioactive peptides based on deep analysis of VEGFR2-binding domain of KIF13B that compete specifically with VEGFR2 binding of KIF13B and thereby potently inhibit angiogenesis. Expression of these peptides by lentivirus prevents VEGF-induced capillary network formation in Matrigel plugs and neovascularization in vivo. A synthetic soluble, cell-permeable, 23–amino acid peptide termed kinesin-derived angiogenesis inhibitor (KAI) not only prevents interaction of VEGFR2 with KIF13B but also trafficking of VEGFR2 in the plus-end direction to the EC plasmalemma. Kinesin-derived angiogenesis inhibitor also inhibits VEGF-induced EC migration and tumor growth in human lung carcinoma xenografted in immunodeficient mice. Thus, we describe a novel class of peptides derived from the site of interaction of KIF13B with VEGFR2 that inhibit VEGFR2 trafficking and thereby starve cancer of blood supply.