Antiangiogenic Therapeutic Potential of Peptides Derived from the Molecular Motor KIF13B that Transports VEGFR2 to Plasmalemma in Endothelial Cells
| Autor: | Asrar B. Malik, Hojin Kang, Kaori H. Yamada |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Matrigel Angiogenesis Cell growth Kinase insert domain receptor respiratory system Biology Molecular biology Pathology and Forensic Medicine Angiogenesis inhibitor Cell biology Neovascularization Vascular endothelial growth factor 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry cardiovascular system medicine Kinesin medicine.symptom circulatory and respiratory physiology |
| Zdroj: | The American Journal of Pathology. 187:214-224 |
| ISSN: | 0002-9440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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