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.