Despite the strong possibility that the endothelial cells (ECs) of tumors and normal tissues may differ in various aspects, most previous studies on ECs have used normal cells. Here, we purified ECs from tumorous and normal human breast tissues, and studied the effect of radiation on angiogenesis and the relevant molecular mechanisms in these cells. We found that in normal tissue-derived endothelial cells (NECs), 4 Gy irradiation increased tube formation, MMP-2 expression and ERK pathway activation. In cancer-derived endothelial cells (CECs), however, 4 Gy irradiation significantly reduced tube formation, increased the production of angiostatin and interleukin-6 (IL-6), and up-regulated AKT and JNK pathway activation. Knockdown experiments showed that siMMP-2 efficiently inhibited tube formation by irradiated NECs, while siPlasminogen effectively attenuated the irradiation-induced suppression of tube formation and the up-regulation of angiostatin in CECs. Moreover, siIL-6 clearly inhibited the irradiation-induced generation of angiostatin in CECs. Inhibition of ERK with a pharmacological inhibitor or siRNAs markedly suppressed irradiation-induced tube formation and MMP-2 up-regulation in NECs, while the inhibition of either AKT or JNK with pharmacological inhibitor or siRNA treatment of CECs clearly attenuated the irradiation-induced inhibition of tube formation and the up-regulation of angiostatin and IL-6. These observations collectively demonstrate that there are distinct differences in the radiation responses of NECs and CECs, and might provide important clues for improving the efficacy of radiation therapy.

Citation Format: Eun-Taex Oh, Moon-Taek Park, Min-Jeong Song, Hyemi Lee, Heon Joo Park. Radiation-induced angiogenic signaling pathway in endothelial cells isolated from normal and cancer tissue of human breast. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3905. doi:10.1158/1538-7445.AM2013-3905

©2013 American Association for Cancer Research
2013