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

被引：856

作者：

Bhat, Krishna P. L. ^{[1
]}

Balasubramaniyan, Veerakumar ^{[5
]}

Vaillant, Brian ^{[7
]}

Ezhilarasan, Ravesanker ^{[2
]}

Hummelink, Karlijn ^{[1
]}

Hollingsworth, Faith ^{[1
]}

Wani, Khalida ^{[1
]}

Heathcock, Lindsey ^{[1
]}

James, Johanna D. ^{[1
]}

Goodman, Lindsey D. ^{[2
]}

Conroy, Siobhan ^{[6
]}

Long, Lihong ^{[1
]}

Lelic, Nina ^{[8
]}

Wang, Suzhen ^{[3
]}

Gumin, Joy ^{[4
]}

Raj, Divya ^{[5
]}

Kodama, Yoshinori ^{[9
]}

Raghunathan, Aditya ^{[10
]}

Olar, Adriana ^{[1
]}

Joshi, Kaushal ^{[11
]}

Pelloski, Christopher E. ^{[12
]}

Heimberger, Amy ^{[4
]}

Kim, Se Hoon ^{[13
]}

Cahill, Daniel P. ^{[8
]}

Rao, Ganesh ^{[4
]}

Den Dunnen, Wilfred F. A. ^{[6
]}

Boddeke, Hendrikus W. G. M. ^{[5
]}

Phillips, Heidi S. ^{[14
]}

Nakano, Ichiro ^{[11
]}

Lang, Frederick F. ^{[4
]}

Colman, Howard ^{[15
,16
]}

Sulman, Erik P. ^{[2
]}

Aldape, Kenneth ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, NL-9713 AV Groningen, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands

[7] Seton Brain & Spine Inst, Dept Neurol, Austin, TX 78701 USA

[8] Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurosurg, Boston, MA 02114 USA

[9] Natl Hosp Org, Osaka Natl Hosp, Div Pathol, Chuo Ku, Osaka 5400006, Japan

[10] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA

[11] Ohio State Univ, Dept Neurosurg, Columbus, OH 43210 USA

[12] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA

[13] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea

[14] Genentech Inc, Dept Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA

[15] Univ Utah, Dept Neurosurg, Salt Lake City, UT 84132 USA

[16] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84132 USA

来源：

CANCER CELL | 2013年 / 24卷 / 03期

关键词：

STEM-CELLS; INITIATING CELLS; GLIOMA; EXPRESSION; HETEROGENEITY; MODULATION; MICROGLIA; PROGNOSIS; MUTATION; BIOLOGY;

D O I：

10.1016/j.ccr.2013.08.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：331 / 346

页数：16

共 54 条

[1] Chemokine signaling via the CXCR2 receptor reinforces senescence [J].

Acosta, Juan C. ;

O'Loghlen, Ana ;

Banito, Ana ;

Guijarro, Maria V. ;

Augert, Arnaud ;

Raguz, Selina ;

Fumagalli, Marzia ;

Da Costa, Marco ;

Brown, Celia ;

Popov, Nikolay ;

Takatsu, Yoshihiro ;

Melamed, Jonathan ;

di Fagagna, Fabrizio d'Adda ;

Bernard, David ;

Hernando, Eva ;

Gil, Jesus .

CELL, 2008, 133 (06) :1006-1018

[2] Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].

Bao, Shideng ;

Wu, Qiulian ;

McLendon, Roger E. ;

Hao, Yueling ;

Shi, Qing ;

Hjelmeland, Anita B. ;

Dewhirst, Mark W. ;

Bigner, Darell D. ;

Rich, Jeremy N. .

NATURE, 2006, 444 (7120) :756-760

[3] Inflammation meets cancer, with NF-κB as the matchmaker [J].

Ben-Neriah, Yinon ;

Karin, Michael .

NATURE IMMUNOLOGY, 2011, 12 (08) :715-723

[4] The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma [J].

Bhat, Krishna P. L. ;

Salazar, Katrina L. ;

Balasubramaniyan, Veerakumar ;

Wani, Khalida ;

Heathcock, Lindsey ;

Hollingsworth, Faith ;

James, Johanna D. ;

Gumin, Joy ;

Diefes, Kristin L. ;

Kim, Se Hoon ;

Turski, Alice ;

Azodi, Yasaman ;

Yang, Yuhui ;

Doucette, Tiffany ;

Colman, Howard ;

Sulman, Erik P. ;

Lang, Frederick F. ;

Rao, Ganesh ;

Copray, Sjef ;

Vaillant, Brian D. ;

Aldape, Kenneth D. .

GENES & DEVELOPMENT, 2011, 25 (24) :2594-2609

[5] Tumor necrosis factor-α-induced protein 3 as a putative regulator of nuclear factor-κB-mediated resistance to O6-alkylating agents in human glioblastomas [J].

Bredel, M ;

Bredel, C ;

Juric, D ;

Duran, GE ;

Yu, RX ;

Harsh, GR ;

Vogel, H ;

Recht, LD ;

Scheck, AC ;

Sikic, BI .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (02) :274-287

[6] NFKBIA Deletion in Glioblastomas. [J].

Bredel, Markus ;

Scholtens, Denise M. ;

Yadav, Ajay K. ;

Alvarez, Angel A. ;

Renfrow, Jaclyn J. ;

Chandler, James P. ;

Yu, Irene L. Y. ;

Carro, Maria S. ;

Dai, Fangping ;

Tagge, Michael J. ;

Ferrarese, Roberto ;

Bredel, Claudia ;

Phillips, Heidi S. ;

Lukac, Paul J. ;

Robe, Pierre A. ;

Weyerbrock, Astrid ;

Vogel, Hannes ;

Dubner, Steven ;

Mobley, Bret ;

He, Xiaolin ;

Scheck, Adrienne C. ;

Sikic, Branimir I. ;

Aldape, Kenneth D. ;

Chakravarti, Arnab ;

Harsh, Griffith R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (07) :627-637

[7] Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory? [J].

Brescia, Paola ;

Richichi, Cristina ;

Pelicci, Giuliana .

JOURNAL OF ONCOLOGY, 2012, 2012

[8] The transcriptional network for mesenchymal transformation of brain tumours [J].

Carro, Maria Stella ;

Lim, Wei Keat ;

Alvarez, Mariano Javier ;

Bollo, Robert J. ;

Zhao, Xudong ;

Snyder, Evan Y. ;

Sulman, Erik P. ;

Anne, Sandrine L. ;

Doetsch, Fiona ;

Colman, Howard ;

Lasorella, Anna ;

Aldape, Ken ;

Califano, Andrea ;

Iavarone, Antonio .

NATURE, 2010, 463 (7279) :318-U68

[9] The Brain Tumor Microenvironment [J].

Charles, Nikki A. ;

Holland, Eric C. ;

Gilbertson, Richard ;

Glass, Rainer ;

Kettenmann, Helmut .

GLIA, 2011, 59 (08) :1169-1180

[10] Malignant Glioma: Lessons from Genomics, Mouse Models, and Stem Cells [J].

Chen, Jian ;

Mckay, Renee M. ;

Parada, Luis F. .

CELL, 2012, 149 (01) :36-47

← 1 2 3 4 5 6 →