Roles of RhoA, RhoC and RhoG in Secretion of Vascular Endothelial Growth Factor (VEGF) by Astrocytoma Cells and Angiogenesis in Vascular Endothelial Cells. (c2015)

Abstract

As the tumor size increases, cancer cells stimulate neighboring vascular endothelial cells to proliferate and form new blood vessels in order to irrigate the tumor. This is through the secretion of vascular endothelial growth factors (VEGF) by the cancer cells that stimulate angiogenesis in vascular endothelial cells. The Rho GTPase family of proteins regulates VEGF secretion by cancer cells and regulates angiogenesis in vascular endothelial cells. Our study aims to elucidate the role of different isoforms of Rho GTPases in Astrocytoma cell expression of VEGF and blood vessels formation in vascular endothelial cells. The role of Rho GTPases in angiogenesis signaling was first examined in vascular endothelial cells. In ECV cells, the knock down of RhoA, RhoC and RhoG reduced the blood tubes formation. Knocking down StarD13, a RhoA and Cdc42 GAP, led to increase in angiogenesis and blood vessel formation. Second, the role of RhoA and RhoC on VEGF levels of expression on Astrocytoma cells was studied; results showed that RhoA regulated VEGF expression more efficiently than RhoC. The role of the PI3K pathway and VEGF secretion in SF268 Astrocytoma cells in response to EGF stimulation or in response to starvation was examined. The study showed that as the cancer cells are deprived from their physiological conditions for a longer period of time as they express more VEGF, MMP-2 and MMP-9. In addition, PI3K pathway is activated after EGF stimulation in tumor cells. In conclusion, this study will explicate the cross-talk between Astrocytoma cells and vascular endothelial cells and the pathways responsible for angiogenesis development