Angiogenic signaling aberrantly induced by tumor hypoxia

Front Biosci (Landmark Ed). 2011 Jan 1;16:31-48. doi: 10.2741/3674.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenomedullin / physiology
  • Angiogenesis Inhibitors / physiology
  • Angiopoietin-2 / physiology
  • Animals
  • Bone Marrow Cells / physiology
  • Chemokines / physiology
  • Cyclooxygenase 2 / physiology
  • Endothelins / physiology
  • Fibroblast Growth Factor 2 / physiology
  • Humans
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1 / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1 / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Matrix Metalloproteinases / physiology
  • Membrane Proteins / physiology
  • NF-kappa B / physiology
  • Neoplasms / blood supply
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / physiopathology*
  • Nitric Oxide Synthase / physiology
  • Placenta Growth Factor
  • Plasminogen Activator Inhibitor 1 / physiology
  • Pregnancy Proteins / physiology
  • Proto-Oncogene Proteins c-sis / physiology
  • Stem Cell Factor / physiology
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Angiogenesis Inhibitors
  • Angiopoietin-2
  • Chemokines
  • Endothelins
  • Hypoxia-Inducible Factor 1
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NF-kappa B
  • PGF protein, human
  • Plasminogen Activator Inhibitor 1
  • Pregnancy Proteins
  • Proto-Oncogene Proteins c-sis
  • Stem Cell Factor
  • Vascular Endothelial Growth Factor A
  • delta protein
  • Fibroblast Growth Factor 2
  • Placenta Growth Factor
  • Adrenomedullin
  • Nitric Oxide Synthase
  • Cyclooxygenase 2
  • Matrix Metalloproteinases