VEGFs and receptors involved in angiogenesis versus lymphangiogenesis

Curr Opin Cell Biol. 2009 Apr;21(2):154-65. doi: 10.1016/j.ceb.2008.12.012. Epub 2009 Feb 21.

Abstract

Vascular endothelial growth factors and their endothelial tyrosine kinase receptors are central regulators of vasculogenesis, angiogenesis and lymphangiogenesis. VEGF signalling through VEGFR-2 is the major angiogenic pathway, and blockage of VEGF/VEGFR-2 signalling is the first anti-angiogenic strategy for cancer therapy. VEGFR-1 seems to act as a negative regulator of VEGF-mediated angiogenesis during development, and as a stimulator of pathological angiogenesis when activated by its specific ligands PlGF and VEGF-B. PlGF recruits angiogenic macrophages to tumours, and targeting PlGF could therefore be beneficial in cancer. For VEGF-B, with very limited angiogenic potential, a new role has been identified in regulating lipid metabolism in the heart. VEGF-C and VEGF-D induce lymphangiogenesis via VEGFR-3 and have also been shown to be lymphangiogenic in tumours, stimulating metastasis. Mouse models of lymphoedema have established VEGF-C as a promising agent for pro-lymphangiogenic therapy. In addition to lymphangiogenesis, VEGFR-3 has also been shown to be important for angiogenesis, acting together with VEGF/VEGFR-2 and Dll4/Notch signalling to control angiogenic sprouting. Increasing knowledge of the mechanisms regulating (lymph)angiogenesis should enable the development of better agents to combat metastasis and the resistance of tumours towards anti-angiogenic treatment, and of pro-(lymph)angiogenic treatment methods for ischaemic diseases and lymphoedema.

Publication types

  • Review

MeSH terms

  • Angiopoietin-1 / metabolism
  • Animals
  • Humans
  • Lymphangiogenesis / physiology*
  • Lymphatic Metastasis
  • Membrane Proteins / metabolism
  • Myocytes, Cardiac / physiology
  • Neovascularization, Physiologic / physiology*
  • Protein Isoforms / metabolism*
  • Receptor, TIE-2 / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factors / metabolism*

Substances

  • Angiopoietin-1
  • Membrane Proteins
  • PIGF protein, human
  • Protein Isoforms
  • Vascular Endothelial Growth Factors
  • Receptor, TIE-2
  • Receptors, Vascular Endothelial Growth Factor