title: Angiogenic signaling aberrantly induced by tumor hypoxia.
abstract: Tumor growth, invasion and metastasis are largely dependent on the development of tumor vasculature. A great number of pro- and antiangiogenic molecules, have been identified. Bone marrow-derived cells are mobilized and recruited to angiogenic sites, by a variety of growth factors and cytokines, to promote angiogenesis and the formation of new blood vessels. The hypoxic microenvironment that is inevitably generated in solid tumors is a major contributor to tumor angiogenesis. Tumor hypoxia aberrantly modulates the expression of many potent pro- and antiangiogenic molecules, primarily through the action of heterodimeric transcription factors termed hypoxia-inducible factors, HIF-1 and HIF-2. The disruption of the balance between pro- and antiangiogenic activities eventually leads to a shift in balance to a more angiogenic state. These findings have provoked considerable interest in HIFs as attractive targets for cancer therapy. Consequently, the development of small molecule HIF inhibitors is currently moving ahead at a fast pace.
authors.affiliation: Department of Life Science, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo 693-8501, Japan. biokeizo@med.shimaneu.ac.j
authors.forename: Keizo
authors.initials: K
authors.lastname: Takenaga
mesh_terms: D053607:Adrenomedullin / Q000502:physiology; D020533:Angiogenesis Inhibitors / Q000502:physiology; D042702:Angiopoietin-2 / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D018925:Chemokines / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D016232:Endothelins / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D000072483:Placenta Growth Factor; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D011257:Pregnancy Proteins / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D019089:Stem Cell Factor / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D018925:Chemokines; D016232:Endothelins; D051793:Hypoxia-Inducible Factor 1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; C000608036:PGF protein, human; D017395:Plasminogen Activator Inhibitor 1; D011257:Pregnancy Proteins; D020574:Proto-Oncogene Proteins c-sis; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; C064045:delta protein; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; D053607:Adrenomedullin; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases