Pro-angiogenic effects of X-rays on murine endothelial cells

Abstract

Recently, significant attention has been paid to the possibility of thwarting cancer progression by inhibition of neoangiogenesis (formation of new blood vessels) in growing tumors. Although general mechanisms of angiogenesis have been elucidated, virtually nothing is known about the effects of low doses of ionizing radiation on pro-angiogenic properties of endothelial cells. In the present study, we evaluated the effects of a low (0.2 Gy), intermediate (1 Gy), and high (4 Gy) doses of X-rays on a few angiogenesis-related parameters of isolated murine endothelial cells. We show here that 24 to 48 hours after irradiation with 0.2 Gy the cell proliferation was inhibited to a similar extent as after the exposure to 1 Gy. Also, adhesion of the 0.2 Gy-irradiated cells to both gelatin and Matrigel ® was inhibited 24 hours post-exposure, whereas irradiation with 1 or 4 Gy resulted in the increased adhesion of the cells to these substrata. Similar effects were observed during the wound migration assay. Finally, 24 hours after exposure of the cells to 0.2 Gy of X-rays, the surface expression of the β3 integrin subunit was down-regulated, whereas irradiations with 1 and 4 Gy of X-rays resulted in the significantly elevated expression of this subunit. These results indicate that proliferating endothelial cells are sensitive in vitro to relatively low doses of ionizing radiation and that the effects of a low dose are opposite to those observed after irradiations with 1 and 4 Gy of X-rays.