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

Authors :
Bhat KPL
Balasubramaniyan V
Vaillant B
Ezhilarasan R
Hummelink K
Hollingsworth F
Wani K
Heathcock L
James JD
Goodman LD
Conroy S
Long L
Lelic N
Wang S
Gumin J
Raj D
Kodama Y
Raghunathan A
Olar A
Joshi K
Pelloski CE
Heimberger A
Kim SH
Cahill DP
Rao G
Den Dunnen WFA
Boddeke HWGM
Phillips HS
Nakano I
Lang FF
Colman H
Sulman EP
Aldape K
Source :
Cancer cell [Cancer Cell] 2013 Sep 09; Vol. 24 (3), pp. 331-46. Date of Electronic Publication: 2013 Aug 29.
Publication Year :
2013

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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-3686
Volume :
24
Issue :
3
Database :
MEDLINE
Journal :
Cancer cell
Publication Type :
Academic Journal
Accession number :
23993863
Full Text :
https://doi.org/10.1016/j.ccr.2013.08.001