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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.

Original publication

DOI

10.1038/ncomms1786

Type

Journal article

Journal

Nat Commun

Publication Date

17/04/2012

Volume

3

Keywords

Animals, Cell Hypoxia, Cell Line, Tumor, Cell Movement, Cell Survival, Humans, Hypoxia-Inducible Factor 1, Male, Mice, Mice, Inbred BALB C, Neoplasms, Radiation Tolerance, Tumor Cells, Cultured, Xenograft Model Antitumor Assays