Details

Autor(en) / Beteiligte

• Moeller, Benjamin J
• Cao, Yiting
• Li, Chuan Y
• Dewhirst, Mark W

Titel

Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules

Ist Teil von

• Cancer cell, 2004-05, Vol.5 (5), p.429-441

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.