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

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-?/NF-?B-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-?B activation correlate with poor radiation response and shorter survival in patients with GBM.

SUBMITTER: Bhat KPL 

PROVIDER: S-EPMC3817560 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature