Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma

Academic Article

Abstract

  • Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here weshow 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. © 2013 Elsevier Inc.
  • Published In

  • Cancer Cell  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 16799004
  • Author List

  • Bhat KPL; Balasubramaniyan V; Vaillant B; Ezhilarasan R; Hummelink K; Hollingsworth F; Wani K; Heathcock L; James JD; Goodman LD
  • Start Page

  • 331
  • End Page

  • 346
  • Volume

  • 24
  • Issue

  • 3