Research Abstract


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

2012年4月17日 Nature Communications 3 : 783 doi: 10.1038/ncomms1786


原田 浩1,2, 井上 正宏3, 板坂 聡2, 広田 喜一4, 森鳰 章代1, 篠宮 和美1, 曽 麗華1,2,5, Guangfei Ou2, 朱 宇熹1,2, 吉村 通央2,6, W. Gillies McKenna6, Ruth J. Muschel6 & 平岡 真寛2

  1. 京都大学生命科学系キャリアパス形成ユニット
  2. 京都大学医学部附属病院 放射線治療科
  3. 大阪府立成人病センター 生化学部門
  4. 京都大学医学部附属病院 麻酔科
  5. Fourth Military Medical University(中国)
  6. オックスフォード大学(英国)
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.