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
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..View full abstract
This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (to M. G. A. and S. A. S.) and the Operational Infrastructure Support Program of the Victorian Government. M. G. A. and S. A. S. are shareholders in Opthea Ltd. and are Inventors on patents assigned to Vegenics Pty. Ltd.