Journal
CANCER CELL
Volume 24, Issue 3, Pages 331-346Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2013.08.001
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Funding
- Caroline Ross Endowment Fellowship
- American Brain Tumor Association Basic Research Fellowship
- Odyssey Special Fellowship
- MDACC Brain Tumor SPORE Career Development grant
- Brain Tumor Funders' Collaborative
- Dr. Marnie Rose Foundation
- National Brain Tumor Society
- V Foundation
- NIH/NCI [P50CA127001, R01-CA1208113]
- Huntsman Cancer Foundation
- Ben and Cathy Ivy Foundation Research Award
- SPORE Animal Core grant
- Dutch Cancer Society [RUG 2011-5150]
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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 nnesenchymal (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-alpha/NF-kappa 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-kappa B activation correlate with poor radiation response and shorter survival in patients with GBM.
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