Positive and Negative Modulation of Angiogenesis by VEGFR1 Ligands

Yihai Cao^*

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

Gloss: In order to grow beyond a mass that can be supported by diffusion to and from the vasculature of surrounding normal tissue, tumors must acquire their own blood supply. Abnormal vascularization also contributes to a range of nonmalignant diseases. The vascular endothelial growth factor (VEGF) family of five growth factors and three associated transmembrane receptor tyrosine kinases (VEGFR1, 2, and 3) are key modulators of normal and pathogenic angiogenic and vasculogenic processes. VEGF-A, when signaling through VEGFR2, is a potent mitogen for vascular endothelial cells. Targeting VEGF-A–mediated signaling is one treatment for several common cancers, although the benefits are currently modest. This Review, which contains four figures and 132 references, discusses the effect of placental growth factor (PlGF) and VEGF-B, two VEGF family members that bind exclusively to VEGFR1, on angiogenic processes and examines the possibility that concurrent targeting of VEGF-A and PlGF might improve the clinical effectiveness of antiangiogenic therapy in the treatment of malignant and nonmalignant diseases.

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

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