Sphingosine 1-phosphate induces vesicular endothelial growth factor expression in endothelial cells

Abstract

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that Gαi/o-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migration by upregulating the expression of VEGF mRNA. [BMB reports 2009; 42(10): 685-690]

Extracellular and intracellular sphingosine-1-phosphate in cancer

“…Hypoxia also induces the release of S1P from tumor cells, including glioma [41], prostate [222], breast cancer [222], and adenocarcinoma cells [223]. Released S1P is a robust pro-angiogenic factor that stimulates angiogenesis directly [224], as well as indirectly through activation of VEGF expression [225]. The upregulation of VEGF expression by S1P is mediated by ZNF580, a C2H2 zinc finger transcription factor important in angiogenesis [226].…”

Lipid phosphate phosphatases and their roles in mammalian physiology and pathology

“…S1P increases endothelial cell migration and angiogenesis ( 64,115 ). It does this directly through S1P 1 receptors ( 116 ), by promoting transactivation of VEGF receptors ( 117 ) and by increasing VEGF release (118)(119)(120)(121). S1P also shows a critical role in maintaining endothelial barrier integrity by stabilizing tight and adherent junctions between cells ( 122 ).…”

α‐Tocopheryl phosphate—An activated form of vitamin E important for angiogenesis and vasculogenesis?

“…94 and 95). Similar to sphingosine-1-phosphate which activates the sphingosine-1-phosphate receptor leading to activation of AP1 (c-jun/c-fos) and VEGF expression [96], aTP could bind to a specific receptor and stimulate VEGF expression.…”