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      Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma.

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          Abstract

          Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM.

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          Author and article information

          Journal
          Cancer Cell
          Cancer cell
          Elsevier BV
          1878-3686
          1535-6108
          Sep 09 2013
          : 24
          : 3
          Affiliations
          [1 ] Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
          [2 ] Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, 9713 AV, The Netherlands.
          [3 ] Seton Brain and Spine Institute, Austin, TX 78701, USA.
          [4 ] Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
          [5 ] Deparment of Neurosurgery, Massachusetts General Hospital/Brain Tumor Center, Boston, MA 02114, USA.
          [6 ] Department of Neuro-oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
          [7 ] Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
          [8 ] Division of Pathology, Osaka National Hospital, National Hospital Organization, Chuo-ku, Osaka 540-0006, Japan.
          [9 ] Department of Pathology, Henry Ford Hospital, Detroit, MI, 48202, USA.
          [10 ] Department of Neurosurgery, The Ohio State University, Columbus, OH 43210, USA.
          [11 ] Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA.
          [12 ] Department of Pathology, Yonsei University College of Medicine, Seoul, 120-752, Korea.
          [13 ] Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
          [14 ] Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, CA 94080, USA.
          [15 ] Department of Neurosurgery, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA.
          Article
          NIHMS516415
          10.1016/j.ccr.2013.08.001
          3817560
          23993863
          5cb9c97b-f96f-4f34-b1fa-9bb82388166f
          Copyright © 2013 Elsevier Inc. All rights reserved.
          History

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