| Literature DB >> 23993863 |
Krishna P L Bhat1, Veerakumar Balasubramaniyan2, Brian Vaillant3, Ravesanker Ezhilarasan4, Howard Colman5, Erik P Sulman4, Kenneth Aldape1, Karlijn Hummelink1, Faith Hollingsworth1, Khalida Wani1, Lindsey Heathcock1, Johanna D James1, Lindsey D Goodman4, Siobhan Conroy2, Lihong Long1, Nina Lelic6, Suzhen Wang7, Joy Gumin8, Divya Raj2, Yoshinori Kodama9, Aditya Raghunathan10, Adriana Olar1, Kaushal Joshi11, Christopher E Pelloski12, Amy Heimberger8, Se Hoon Kim13, Daniel P Cahill6, Ganesh Rao8, Wilfred F A Den Dunnen14, Hendrikus W G M Boddeke2, Heidi S Phillips15, Ichiro Nakano11, Frederick F Lang8.
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.Entities:
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Year: 2013 PMID： 23993863 PMCID： PMC3817560 DOI： 10.1016/j.ccr.2013.08.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743