Radiation-induced angiogenic signaling pathway in endothelial cells obtained from normal and cancer tissue of human breast.

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