Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels

作者：Hiroshi Harada, Masahiro Inoue, Satoshi Itasaka, Kiichi Hirota, Akiyo Morinibu, Kazumi Shinomiya, Lihua Zeng, Guangfei Ou, Yuxi Zhu, Michio Yoshimura, W. Gillies McKenna, Ruth J. Muschel, Masahiro Hiraoka · 发表于：Nature Communications · 年份：2012 · DOI：10.1038/ncomms1786 · 被引用次数：178 · 研究领域：Cancer, Hypoxia, and Metabolism、Cancer Research and Treatments、Cancer Cells and Metastasis

Tumour recurrence frequently occurs after radiotherapy, but the characteristics, intratumoural localization and post-irradiation behaviour of radioresistant cancer cells remain largely unknown. Here we develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic regions at the time of radiation. Although the perinecrotic tumour cells are originally hypoxia-inducible factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their translocation towards tumour blood vessels. HIF-1 inhibitors suppress the translocation and decrease the incidence of post-irradiation tumour recurrence. For the first time, our data unveil the HIF-1-dependent cellular dynamics during post-irradiation tumour recurrence and provide a rational basis for targeting HIF-1 after radiation therapy. Radiotherapy is used to treat many cancers but radiation-resistant cells can result in recurrence of the tumour. Here, Harada and colleagues develop a method to track cells that persist after radiation treatment and show that the cells acquire transcriptional activity of HIF-1 and move towards blood vessels.