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

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 JoshiChristopher E. Pelloski, Amy Heimberger, Se Hoon Kim, Daniel P. Cahill, Ganesh Rao, Wilfred F.A. DenDunnen, Hendrikus W.G.M. Boddeke, Heidi S. Phillips, Ichiro Nakano, Frederick F. Lang, Howard Colman, Erik P. Sulman, Kenneth Aldape

Research output: Contribution to journalArticle

359 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)331-346
Number of pages16
JournalCancer Cell
Volume24
Issue number3
DOIs
StatePublished - Sep 9 2013
Externally publishedYes

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Glioblastoma
Glioma
Radiation
Tumor Microenvironment
Microglia
Macrophages
Phenotype
Survival
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Bhat, K. P. L., Balasubramaniyan, V., Vaillant, B., Ezhilarasan, R., Hummelink, K., Hollingsworth, F., ... Aldape, K. (2013). Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma. Cancer Cell, 24(3), 331-346. https://doi.org/10.1016/j.ccr.2013.08.001

Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma. / Bhat, Krishna P.L.; Balasubramaniyan, Veerakumar; Vaillant, Brian; Ezhilarasan, Ravesanker; Hummelink, Karlijn; Hollingsworth, Faith; Wani, Khalida; Heathcock, Lindsey; James, Johanna D.; Goodman, Lindsey D.; Conroy, Siobhan; Long, Lihong; Lelic, Nina; Wang, Suzhen; Gumin, Joy; Raj, Divya; Kodama, Yoshinori; Raghunathan, Aditya; Olar, Adriana; Joshi, Kaushal; Pelloski, Christopher E.; Heimberger, Amy; Kim, Se Hoon; Cahill, Daniel P.; Rao, Ganesh; DenDunnen, Wilfred F.A.; Boddeke, Hendrikus W.G.M.; Phillips, Heidi S.; Nakano, Ichiro; Lang, Frederick F.; Colman, Howard; Sulman, Erik P.; Aldape, Kenneth.

In: Cancer Cell, Vol. 24, No. 3, 09.09.2013, p. 331-346.

Research output: Contribution to journalArticle

Bhat, KPL, Balasubramaniyan, V, Vaillant, B, Ezhilarasan, R, Hummelink, K, Hollingsworth, F, Wani, K, Heathcock, L, James, JD, Goodman, LD, Conroy, S, Long, L, Lelic, N, Wang, S, Gumin, J, Raj, D, Kodama, Y, Raghunathan, A, Olar, A, Joshi, K, Pelloski, CE, Heimberger, A, Kim, SH, Cahill, DP, Rao, G, DenDunnen, WFA, Boddeke, HWGM, Phillips, HS, Nakano, I, Lang, FF, Colman, H, Sulman, EP & Aldape, K 2013, 'Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma', Cancer Cell, vol. 24, no. 3, pp. 331-346. https://doi.org/10.1016/j.ccr.2013.08.001
Bhat KPL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F et al. Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma. Cancer Cell. 2013 Sep 9;24(3):331-346. https://doi.org/10.1016/j.ccr.2013.08.001
Bhat, Krishna P.L. ; Balasubramaniyan, Veerakumar ; Vaillant, Brian ; Ezhilarasan, Ravesanker ; Hummelink, Karlijn ; Hollingsworth, Faith ; Wani, Khalida ; Heathcock, Lindsey ; James, Johanna D. ; Goodman, Lindsey D. ; Conroy, Siobhan ; Long, Lihong ; Lelic, Nina ; Wang, Suzhen ; Gumin, Joy ; Raj, Divya ; Kodama, Yoshinori ; Raghunathan, Aditya ; Olar, Adriana ; Joshi, Kaushal ; Pelloski, Christopher E. ; Heimberger, Amy ; Kim, Se Hoon ; Cahill, Daniel P. ; Rao, Ganesh ; DenDunnen, Wilfred F.A. ; Boddeke, Hendrikus W.G.M. ; Phillips, Heidi S. ; Nakano, Ichiro ; Lang, Frederick F. ; Colman, Howard ; Sulman, Erik P. ; Aldape, Kenneth. / Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma. In: Cancer Cell. 2013 ; Vol. 24, No. 3. pp. 331-346.
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AU - Hummelink, Karlijn

AU - Hollingsworth, Faith

AU - Wani, Khalida

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AU - James, Johanna D.

AU - Goodman, Lindsey D.

AU - Conroy, Siobhan

AU - Long, Lihong

AU - Lelic, Nina

AU - Wang, Suzhen

AU - Gumin, Joy

AU - Raj, Divya

AU - Kodama, Yoshinori

AU - Raghunathan, Aditya

AU - Olar, Adriana

AU - Joshi, Kaushal

AU - Pelloski, Christopher E.

AU - Heimberger, Amy

AU - Kim, Se Hoon

AU - Cahill, Daniel P.

AU - Rao, Ganesh

AU - DenDunnen, Wilfred F.A.

AU - Boddeke, Hendrikus W.G.M.

AU - Phillips, Heidi S.

AU - Nakano, Ichiro

AU - Lang, Frederick F.

AU - Colman, Howard

AU - Sulman, Erik P.

AU - Aldape, Kenneth

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