Neuropilins as common targeting molecules on tumor and endothelial cells to inhibit metastasis

Class 3 semaphorins (SEMA3) are ligands for neuropilins (NRP), which are receptors that mediate axon guidance and angiogenesis signaling. Although seminal studies on SEMA3s and NRPs first showed them to be mediators of axon guidance, it has become very apparent that these proteins play important roles in vascular and tumor biology as well. SEMA3s not only repel neurons and collapse axon growth cones, but have similar effects on endothelial cells and tumor cells. Preclinical studies indicate that NRPs are candidate target molecules of tumor angiogenesis and metastasis. In addition, neutralizing antibodies anti-NRP-1 enhance the effects of anti-VEGF antibodies in suppressing tumor growth in xenograft models. SEMA3F, which binds to NRP-2, inhibits tumor cell migration and angiogenesis. This article reviews the roles of NRP in tumor angiogenesis and metastasis based on cell culture and murine studies.