Vascular endothelial growth factor (VEGF) and its receptors

Abstract

Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. Five VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene. These isoforms differ in their molecular mass and in biological properties such as their ability to bind to cell-surface heparan-sulfate proteoglycans. The expression of VEGF is potentiated in response to hypoxia, by activated oncogenes, and by a variety of cytokines. VEGF induces endothelial cell proliferation, promotes cell migration, and inhibits apoptosis. In vivo VEGF induces angiogenesis as well as permeabilization of blood vessels, and plays a central role in the regulation of vasculogenesis. Deregulated VEGF expression contributes to the development of solid tumors by promoting tumor angiogenesis and to the etiology of several additional diseases that are characterized by abnormal angiogenesis. Consequently, inhibition of VEGF signaling abrogates the development of a wide variety of tumors. The various VEGF forms bind to two tyrosine-kinase receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1), which are expressed almost exclusively in endothelial cells. Endothelial cells express in addition the neuropilin-1 and neuropilin-2 coreceptors, which bind selectively to the 165 amino acid form of VEGF (VEGF165). This review focuses on recent developments that have widened considerably our understanding of the mechanisms that control VEGF production and VEGF signal transduction and on recent studies that have shed light on the mechanisms by which VEGF regulates angiogenesis.

Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth

“…41 Many articles have described that tumor cells mainly express VEGF 121 and VEGF 165 isoforms. 36,42 Our results support these previous reports.…”

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

“…Although hypoxia is the most common inducer of VEGF synthesis, molecules associated with intraocular inflammatory conditions (epidermal growth factor, TGF-␣, TGF-␤, keratinocyte growth factor, insulin-like growth factor 1, FGF, IL-1␣, IL-6, protein kinase C-␤, and platelet-derived growth factor) can up-regulate VEGF messenger RNA synthesis (Figure 1). 26 As both a growth factor and a survival factor, VEGF pursues several different tactics in target tissues ( Figure 2). By stimulating the mitosis and swelling of arterial, venous, and lymphatic endothelial cells, VEGF initiates angiogenesis.…”

Endothelial cell functions

“…VEGFR3 is largely restricted to lymphatic endothelium while VEGFR1 and R2 are expressed by vascular endothelium. VEGFR2 is the main receptor able to induce endothelial cell proliferation as well as migratory and sprouting activity and to help promote endothelial cells to form tubule-like structures (Eriksson and Alitalo, 1999;Neufeld et al, 1999). VEGF is a potent and critical vascular regulator and disruption of one single allele of VEGF leads to embryonic lethality due to severe vascular abnormalities (Carmeliet et al, 1996;Ferrara et al, 1996).…”