The function of Vascular Endothelial Growth Factor in cancer metastasis

Abstract

Cancer metastasis is one of the leading causes of death in humans and animals diagnosed with cancer. It is a complex process that involves the spread of cancer cells from the primary cancer to another parts of the body through lymphatic and blood vessels. Cancer angiogenesis and lymphangiogenesis have been considered as essential processes in the cancer metastasis because the new formation blood and lymphatic vessels occur, thereby creating new route for cancer cells to metastasize. Vascular endothelial growth factors (VEGF) is a protein previously known for the role in promoting vasculogenesis and angiogenesis. Overexpression of VEGF is known to be implicated in a wide variety of disease processes, especially cancer metastatic process. At present, there are 7 members of the VEGF family, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and PlGF. Among all VEGF members, VEGF-A, VEGF-C and VEGF-D have been reported to be capable to promote cancer angiogenesis and lymphangiogenesis. Moreover, the molecular mechanism of VEGFs and their interaction with the VEGF receptors (VEGFRs) which involve in the processes of cancer metastasis has been extensively described in details. The previous research has shown that VEGF-A plays a major role in angiogenesis through the interaction with VEGFR1 and VEGFR2 receptors as well as with neuropilins presented on the endothelial cells. Following the stimulation of several signal transduction pathways, these interaction result in the endothelial cell proliferation and migration, by which subsequently leads to finally the neovascularization. Apart from the role of VEGF-A, in addition to the role of VEGF-A associated with angiogenesis, VEGF-C and VEGF-D have also been recently reported for their major roles in lymphagiogenesis through the interaction with VEGFR3 which is mostly present in lymphatic endothelial cells. Moreover, VEGF-C and VEGF-D are able to promote angiogenesis. Therefore, the inhibition of VEGF-A, VEGF-C, VEGF-D, and VEGFRs might be used in cancer treatment for the reduction in cancer metastasis.