Positive and negative modulation of angiogenesis by VEGFR1 ligands.
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.
Cao
Yihai
Y
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden. yihai.cao@ki.se
D017398:Alternative Splicing / Q000235:genetics; D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
D043924:Angiogenesis Modulating Agents; D008024:Ligands; D008565:Membrane Proteins; C098069:PIGF protein, human; D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1