title: Vascular endothelial growth factor-D: signaling mechanisms, biology, and clinical relevance.
abstract: Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that promotes growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis), and can induce remodeling of large lymphatics. VEGF-D enhances solid tumor growth and metastatic spread in animal models of cancer, and in some human cancers VEGF-D correlates with metastatic spread, poor patient outcome, and, potentially, with resistance to anti-angiogenic drugs. Hence, VEGF-D signaling is a potential target for novel anti-cancer therapeutics designed to enhance anti-angiogenic approaches and to restrict metastasis. In the cardiovascular system, delivery of VEGF-D in animal models enhanced angiogenesis and tissue perfusion, findings which have led to a range of clinical trials testing this protein for therapeutic angiogenesis in cardiovascular diseases. Despite these experimental and clinical developments, our knowledge of the signaling mechanisms driven by VEGF-D is still evolving--here we explore the biology of VEGF-D, its signaling mechanisms, and the clinical relevance of this growth factor.
authors: Peter MacCallum Cancer Centre, 1 Saint Andrews Place, Locked Bag 1, A'Beckett Street, East Melbourne, Victoria 3002, Australia. marc.achen@petermac.org
authors: Marc G
authors: MG
authors: Achen
authors: Steven A
authors: SA
authors: Stacker
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D042643:Vascular Endothelial Growth Factor D / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042643:Vascular Endothelial Growth Factor D; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3