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Cancer Cell. 2013 Sep 9;24(3):331-46. doi: 10.1016/j.ccr.2013.08.001. Epub 2013 Aug 29.

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

Author information

  • 1Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: kbhat@mdanderson.org.

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23993863
[PubMed - indexed for MEDLINE]
PMCID:
PMC3817560
Free PMC Article
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