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

H Harada, M Inoue, S Itasaka, K Hirota… - Nature …, 2012 - nature.com
H Harada, M Inoue, S Itasaka, K Hirota, A Morinibu, K Shinomiya, L Zeng, G Ou, Y Zhu…
Nature communications, 2012nature.com
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 …
Abstract
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.
nature.com