Angiogenesis, Metastasis, and Tumor Micronenvironment HIF-1–Dependent Stromal Adaptation to Ischemia Mediates In Vivo Tumor Radiation Resistance

نویسندگان

  • David L. Schwartz
  • James Bankson
  • Luc Bidaut
  • Yi He
  • Ryan Williams
  • Robert Lemos
  • Arun Kumar Thitai
  • Junghwan Oh
  • Andrei Volgin
  • Suren Soghomonyan
  • Hsin-Hsien Yeh
  • Ryuichi Nishii
  • Uday Mukhopadhay
  • Mian Alauddin
  • Ioseb Mushkudiani
  • Norihito Kuno
  • Sunil Krishnan
  • William Bornman
  • Stephen Y. Lai
  • Garth Powis
  • John Hazle
  • Juri Gelovani
چکیده

Purpose:Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor–stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1–dependent resistance pathways. Methods: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in

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تاریخ انتشار 2011