Vascular endothelial growth factor (VEGF) signaling in tumor progression

Crit Rev Oncol Hematol. 2007 Jun;62(3):179-213. doi: 10.1016/j.critrevonc.2007.01.006. Epub 2007 Feb 26.


Vascular endothelial cells are ordinarily quiescent in adult humans and divide less than once per decade. When tumors reach a size of about 0.2-2.0mm in diameter, they become hypoxic and limited in size in the absence of angiogenesis. There are about 30 endogenous pro-angiogenic factors and about 30 endogenous anti-angiogenic factors. In order to increase in size, tumors undergo an angiogenic switch where the action of pro-angiogenic factors predominates, resulting in angiogenesis and tumor progression. One mechanism for driving angiogenesis results from the increased production of vascular endothelial growth factor (VEGF) following up-regulation of the hypoxia-inducible transcription factor. The human VEGF family consists of VEGF (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases and two non-protein kinase receptors (neuropilin-1 and -2). Owing to the importance of angiogenesis in tumor progression, inhibition of VEGF signaling represents an attractive cancer treatment.

Publication types

  • Review

MeSH terms

  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / physiopathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neuropilins / metabolism
  • Oncogenes / physiology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • Neuropilins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor