Through a poorly understood mechanism, tumors respond to radiation by secreting cytokines capable of inhibiting apoptosis in endothelial cells, thereby diminishing treatment response by minimizing vascular damage. We reveal here that this pathway is governed by a major angiogenesis regulator, HIF-1. Following radiotherapy, tumor reoxygenation leads to: (1) nuclear accumulation of HIF-1 in response to reactive oxygen, and (2) enhanced translation of HIF-1-regulated transcripts secondary to stress granule depolymerization. The resulting increase in HIF-1-regulated cytokines enhances endothelial cell radioresistance. Inhibiting postradiation HIF-1 activation significantly increases tumor radiosensitivity as a result of enhanced vascular destruction. These data describe novel pathways contributing significantly to our understanding of HIF-1 regulation which may be major determinants of tumor radiosensitivity, potentially having high clinical relevance.

中文翻译：

---

辐射激活HIF-1来调节肿瘤中的血管放射敏感性：补氧，自由基和应激颗粒的作用。

通过一个鲜为人知的机制，肿瘤通过分泌能够抑制内皮细胞凋亡的细胞因子来响应放射，从而通过最大程度地减少血管损伤来减少治疗反应。我们在这里揭示此途径受主要的血管生成调节剂，HIF-1。放疗后，肿瘤再充氧导致：（1）HIF-1在反应性氧反应下的核蓄积；（2）继应力颗粒解聚后，HIF-1调控的转录本的翻译增强。HIF-1调节细胞因子的增加导致内皮细胞的放射抗性。由于增强的血管破坏作用，抑制放射后HIF-1激活可显着提高肿瘤的放射敏感性。