Blood vessels are required for the growth and dissemination of a solid tumor. There are numerous growth factors involved in tumor angiogenesis, but foremost among them is the family of vascular endothelial growth factors (VEGFs). The VEGF family includes VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PGF). These ligands bind with different affinities to three endothelial receptor tyrosine kinases (RTKs), such as VEGFR1, VEGFR2, and VEGFR3, as well as co-receptors, including neuropilins and heparan sulfate proteoglycans. VEGFA has been studied more than other family members and is a critical regulator of angiogenesis. VEGFA is usually referred to simply as VEGF. Vascular endothelial growth factor promotes tumor angiogenesis through stimulating the proliferation and survival of endothelial cells and also by increasing the permeability of vessels and recruiting vascular precursor cells from the bone marrow. VEGF has some direct effects on cancer cells or cancer stem cells. VEGF might promote cancer cell proliferation through the activation of VEGFR1 signaling. VEGFA/neuropilin-1 pathway conferred cancer stemness via the activation of the Wnt/β-catenin axis in breast cancer cells, also promotes tumor-initiating cell self-renewal through VEGFR2/STAT3 signaling.


1.Yang J,et al. Front Immunol. 2018;9:978.