Positive and negative modulation of angiogenesis by VEGFR1 ligands

Sci Signal. 2009 Feb 24;2(59):re1. doi: 10.1126/scisignal.259re1.

Abstract

Vascular endothelial growth factor-A (VEGF-A) is a key target for new antiangiogenic drugs for the treatment of both malignant and nonmalignant human diseases. Vascular effects of VEGF family members are mainly mediated by VEGF receptor 2 (VEGFR2). Conversely, the function and signaling of VEGFR1, which is present on endothelial and nonendothelial cells, are poorly understood. Intriguingly, two of five members in the VEGF family--VEGF-B and placental growth factor (PlGF)--are exclusive ligands for VEGFR1 and do not interact with the other VEGFRs, VEGFR2 and VEGFR3. These VEGFR1-specific ligands may be important therapeutic targets for the treatment of cancer. This Review discusses the distinctive roles of VEGFR1 and its ligands PlGF and VEGF-B in the mediation of angiogenic signaling and considers the therapeutic potential of targeting these particular vascular factors.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics
  • Angiogenesis Modulating Agents / metabolism*
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological*
  • Neoplasms / metabolism
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Vascular Endothelial Growth Factor B / genetics
  • Vascular Endothelial Growth Factor B / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*

Substances

  • Angiogenesis Modulating Agents
  • Ligands
  • Membrane Proteins
  • PIGF protein, human
  • Vascular Endothelial Growth Factor B
  • Vascular Endothelial Growth Factor Receptor-1