Positive and Negative Modulation of Angiogenesis by VEGFR1 Ligands

Yihai Cao^*

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.

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.

* Corresponding author. E-mail, yihai.cao{at}ki.se

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