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Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma.
- 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.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Cell Differentiation genetics
Cluster Analysis
DNA Methylation
Disease Models, Animal
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma mortality
Humans
Hyaluronan Receptors genetics
Hyaluronan Receptors metabolism
Mice
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Oligodendrocyte Transcription Factor 2
Prognosis
Signal Transduction
Transcriptome
Tumor Necrosis Factor-alpha pharmacology
Xenograft Model Antitumor Assays
Glioblastoma genetics
Glioblastoma metabolism
NF-kappa B genetics
NF-kappa B metabolism
Radiation Tolerance genetics
Subjects
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