Mesenchymal Differentiation Mediated by NF-¦ÊB Promotes Radiation Resistance in Glioblastoma

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• 作者：Krishna?P.L. Bhat ; Veerakumar Balasubramaniyan ; Brian Vaillant ; Ravesanker Ezhilarasan ; Karlijn Hummelink ; Faith Hollingsworth ; Khalida Wani ; Lindsey Heathcock ; Johanna?D. James ; Lindsey?D. Goodman ; Siobhan Conroy ; Lihong Long ; Nina Lelic ; Suzhen Wang ; Joy Gumin ; Divya Raj ; Yoshinori Kodama ; Aditya Raghunathan ; Adriana Olar ; Kaushal Joshi ; et al.
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：9 September, 2013
• 年：2013
• 卷：24
• 期：3
• 页码：331-346
• 全文大小：5395 K

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Summary

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-¦Á/NF-¦ÊB-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-¦ÊB activation correlate with poor radiation response and shorter survival in patients with GBM.