Neuropilins (NRPs) are multifunctional receptors for class 3 semaphorins, which are responsible for axon guidance during the development of the nervous system in vertebrates, and for vascular endothelial growth factors (VEGFs), essential for vascular development and angiogenesis in disease. There is now a large body of evidence that NRPs also mediate tumour angiogenesis and progression, and they have also emerged as novel therapeutic targets in cancer. Many neoplastic cell types express NRPs, and NRP1 and NRP2 upregulation is positively correlated with tumour progression and poor patient prognosis in several cancer types (Pellet-Many et al. Biochem J 411:211–226, 2008). Recently, NRPs have been shown to play novel roles in the tumour stem cell niche and in regulation of tumour immunity. This chapter focuses on the role of NRPs in tumour angiogenesis and tumour progression, focusing on the role of the NRPs as modulators of VEGF function and highlighting approaches to therapeutic targeting of NRPs in cancer
