PMID- 23993863
OWN - NLM
STAT- MEDLINE
DCOM- 20131211
LR  - 20220316
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 24
IP  - 3
DP  - 2013 Sep 9
TI  - Mesenchymal differentiation mediated by NF-kappaB promotes radiation resistance in 
      glioblastoma.
PG  - 331-46
LID - 10.1016/j.ccr.2013.08.001 [doi]
AB  - 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-alpha/NF-kappaB-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-kappaB activation correlate with poor radiation response and 
      shorter survival in patients with GBM.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Bhat, Krishna P L
AU  - Bhat KPL
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Balasubramaniyan, Veerakumar
AU  - Balasubramaniyan V
AD  - Department of Neuroscience, University of Groningen, University Medical Center 
      Groningen, Groningen, 9713 AV, The Netherlands.
FAU - Vaillant, Brian
AU  - Vaillant B
AD  - Seton Brain and Spine Institute, Austin, TX 78701, USA.
FAU - Ezhilarasan, Ravesanker
AU  - Ezhilarasan R
AD  - Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer 
      Center, Houston, TX 77030, USA.
FAU - Hummelink, Karlijn
AU  - Hummelink K
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Hollingsworth, Faith
AU  - Hollingsworth F
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Wani, Khalida
AU  - Wani K
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Heathcock, Lindsey
AU  - Heathcock L
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - James, Johanna D
AU  - James JD
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Goodman, Lindsey D
AU  - Goodman LD
AD  - Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer 
      Center, Houston, TX 77030, USA.
FAU - Conroy, Siobhan
AU  - Conroy S
AD  - Department of Neuroscience, University of Groningen, University Medical Center 
      Groningen, Groningen, 9713 AV, The Netherlands.
FAU - Long, Lihong
AU  - Long L
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Lelic, Nina
AU  - Lelic N
AD  - Deparment of Neurosurgery, Massachusetts General Hospital/Brain Tumor Center, 
      Boston, MA 02114, USA.
FAU - Wang, Suzhen
AU  - Wang S
AD  - Department of Neuro-oncology, The University of Texas, M.D. Anderson Cancer 
      Center, Houston, TX 77030, USA.
FAU - Gumin, Joy
AU  - Gumin J
AD  - Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Raj, Divya
AU  - Raj D
AD  - Department of Neuroscience, University of Groningen, University Medical Center 
      Groningen, Groningen, 9713 AV, The Netherlands.
FAU - Kodama, Yoshinori
AU  - Kodama Y
AD  - Division of Pathology, Osaka National Hospital, National Hospital Organization, 
      Chuo-ku, Osaka 540-0006, Japan.
FAU - Raghunathan, Aditya
AU  - Raghunathan A
AD  - Department of Pathology, Henry Ford Hospital, Detroit, MI, 48202, USA.
FAU - Olar, Adriana
AU  - Olar A
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Joshi, Kaushal
AU  - Joshi K
AD  - Department of Neurosurgery, The Ohio State University, Columbus, OH 43210, USA.
FAU - Pelloski, Christopher E
AU  - Pelloski CE
AD  - Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, 
      USA.
FAU - Heimberger, Amy
AU  - Heimberger A
AD  - Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Kim, Se Hoon
AU  - Kim SH
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul, 120-752, 
      Korea.
FAU - Cahill, Daniel P
AU  - Cahill DP
AD  - Deparment of Neurosurgery, Massachusetts General Hospital/Brain Tumor Center, 
      Boston, MA 02114, USA.
FAU - Rao, Ganesh
AU  - Rao G
AD  - Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Den Dunnen, Wilfred F A
AU  - Den Dunnen WFA
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
FAU - Boddeke, Hendrikus W G M
AU  - Boddeke HWGM
AD  - Department of Neuroscience, University of Groningen, University Medical Center 
      Groningen, Groningen, 9713 AV, The Netherlands.
FAU - Phillips, Heidi S
AU  - Phillips HS
AD  - Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San 
      Francisco, CA 94080, USA.
FAU - Nakano, Ichiro
AU  - Nakano I
AD  - Department of Neurosurgery, The Ohio State University, Columbus, OH 43210, USA.
FAU - Lang, Frederick F
AU  - Lang FF
AD  - Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Colman, Howard
AU  - Colman H
AD  - Department of Neurosurgery, and Huntsman Cancer Institute, University of Utah, 
      Salt Lake City, UT 84132, USA.
FAU - Sulman, Erik P
AU  - Sulman EP
AD  - Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer 
      Center, Houston, TX 77030, USA.
FAU - Aldape, Kenneth
AU  - Aldape K
AD  - Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
LA  - eng
SI  - GEO/GSE49009
GR  - R01 NS083767/NS/NINDS NIH HHS/United States
GR  - R01 CA120813/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P30-CA016672/CA/NCI NIH HHS/United States
GR  - R21 CA175875/CA/NCI NIH HHS/United States
GR  - P50CA127001/CA/NCI NIH HHS/United States
GR  - K08 NS070928/NS/NINDS NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R01-CA1208113/CA/NCI NIH HHS/United States
GR  - P50 CA127001/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130829
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (NF-kappa B)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (OLIG2 protein, human)
RN  - 0 (Oligodendrocyte Transcription Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Cell Differentiation/genetics
MH  - Cluster Analysis
MH  - DNA Methylation
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/*genetics/*metabolism/mortality
MH  - Humans
MH  - Hyaluronan Receptors/genetics/metabolism
MH  - Mice
MH  - NF-kappa B/*genetics/*metabolism
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Oligodendrocyte Transcription Factor 2
MH  - Prognosis
MH  - Radiation Tolerance/*genetics
MH  - Signal Transduction
MH  - Transcriptome
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Xenograft Model Antitumor Assays
PMC - PMC3817560
MID - NIHMS516415
EDAT- 2013/09/03 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/09/09
CRDT- 2013/09/03 06:00
PHST- 2012/05/11 00:00 [received]
PHST- 2013/06/24 00:00 [revised]
PHST- 2013/08/01 00:00 [accepted]
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/09/09 00:00 [pmc-release]
AID - 10.1016/j.ccr.2013.08.001 [doi]
PST - ppublish
SO  - Cancer Cell. 2013 Sep 9;24(3):331-46. doi: 10.1016/j.ccr.2013.08.001. Epub 2013 
      Aug 29.