Journal article

Differential Receptor Binding and Regulatory Mechanisms for the Lymphangiogenic Growth Factors Vascular Endothelial Growth Factor (VEGF)-C and -D

Natalia Davydova, Nicole C Harris, Sally Roufail, Sophie Paquet-Fifield, Musarat Ishaq, Victor A Streltsov, Steven P Williams, Tara Karnezis, Steven A Stacker, Marc G Achen

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2016

Abstract

VEGF-C and VEGF-D are secreted glycoproteins that induce angiogenesis and lymphangiogenesis in cancer, thereby promoting tumor growth and spread. They exhibit structural homology and activate VEGFR-2 and VEGFR-3, receptors on endothelial cells that signal for growth of blood vessels and lymphatics. VEGF-C and VEGF-D were thought to exhibit similar bioactivities, yet recent studies indicated distinct signaling mechanisms (e.g. tumor-derived VEGF-C promoted expression of the prostaglandin biosynthetic enzyme COX-2 in lymphatics, a response thought to facilitate metastasis via the lymphatic vasculature, whereas VEGF-D did not). Here we explore the basis of the distinct bioactivities of VEGF-D u..

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