There is much evidence that VEGFR-2 (KDR) is the major mediator of VEGFA-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic angiogenesis. In addition, VEGFR-2 binds proteolytically processed VEGFC and VEGFD. VEGFR-2 is expressed in most if not all adult vascular endothelial cells, as well as in circulating endothelial progenitor cells, pancreatic duct cells, retinal progenitor cells, megakaryocytes, and hematopoietic cells. VEGFR-2, often in combination with VEGFR-3, is significantly upregulated in the tumor vascular endothelium in most common human solid tumor types. Tumor cells may also express VEGFR-2, although epithelial and mesenchymal tumor cells typically express VEGFR-1 rather than VEGFR-2. Nevertheless, increased expression of VEGFR-2 on tumor cells has been noted for melanoma and hematological malignancies. It has been shown that VEGFR-2-mediated signaling led to survival of cancer cells under chronic hypoxic conditions and might contribute to a more aggressive phenotype. Growing evidence supports an important link between chronic inflammation and tumor development. Induction of VEGFR-2 expression in tumor cells, and also in intestinal epithelium during colitis, is mediated by the proinflammatory cytokine interleukin 6, which is a strong promoter of tumor growth in experimental colitis-associated colon cancer. sVEGFR-2 has been described and may have important biological roles. sVEGFR-2 binds VEGFC and thus prevents activation of VEGFR-3, consequently inhibiting lymphatic endothelial cell proliferation. Notably, it has been recently shown that downregulation of sVEGFR-2 in advanced metastatic neuroblastoma may promote lymphogenic spread of metastases.
Rapisarda A, Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy[J]. Advances in cancer research, 2011, 114: 237-267.