X-ray and Carbon Ion Beam Irradiation Inhibited Angiogenesis via Integrin Up-regulation

Abstract

Angiogenesis is essential for tumor growth. Control of angiogenesis is expected as a new therapy for cancer. It is possible that a part of effect on radiation therapy for cancer inhibits angiogenesis, but this mechanism is not clear. The purposes of this study was to investigate the effects of radiation on vascular endothelial cells including expression level of integrin family and to compare the effect by X-ray irradiation with carbon ion beam irradiation. Human endothelial cells, HUVEC and ECV304, were irradiated by carbon ion beam at Heavy Ion Medical Accelerator in Chiba and 4MV X-ray. We evaluated the effects of irradiation in cell motility, cell adhesion to extracellular matrix, tube formation and expression of integrin molecules. Both high dose X-ray and carbon ion irradiation decreased cell motility and tube formation. Adhesion abilities of cells irradiated with high dose X-ray and carbon ion beam were up-regulated. Also integrin α6 and β1 which associated with cell-extracellular matrix adhesion were up-regulated with high dose X-ray and carbon ion beam in mRNA and protein level. High dose irradiation of X-ray and carbon ion beam inhibited function of endothelial cells including the cell motility and tube formation, and up-regulated the capabilities of adhesion and the expression of integrin α6 and β1. These results suggest that high dose radiations might inhibit angiogenesis through integrin expression changes.