VEGFR1 (alternatively denoted as Fms-like tyrosine kinase 1, Flt1, in the mouse) is a single-transmembrane glycoprotein. VEGFR1 plays a role in tumor progression and dissemination. Indeed, the rate of tumor growth of melanoma and glioma tumor models is considerably reduced in VEGFR1 TK / mice. In addition, VEGFR1 activity has been shown to play a role in metastatic dissemination, and expression of VEGFR1 in tumor cells seems to increase tumor invasiveness. Furthermore, VEGFR1 has been shown to activate extracellular signal-regulated kinase 1/2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and Src family kinases to mediate growth and migration of human colorectal carcinoma cells. Finally, activation of VEGFR1 in breast cancer cells supports their growth and survival, strongly arguing in favor of the importance of VEGFR1-mediated signaling in these models. Regulation of inflammatory cell recruitment by VEGFR1 appears to be exerted mainly through PIGF. Notably, the expression of PIGF is very low under physiological conditions, but it may be strongly upregulated in various cell types by different pathological stimuli such as hypoxia, inflammatory cytokines, or oncogenes. PIGF has been regarded as an attractive candidate for antiangiogenic therapy. Indeed, it has been shown that PIGF plays a key role in promoting pathological angiogenesis associated with tumor progression, and overexpression of PIGF in a mouse melanoma model resulted in increased tumor growth and metastasis.
Rapisarda A, Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy[J]. Advances in cancer research, 2011, 114: 237-267.