Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity

被引:106
作者
Brown, Daniel V. [1 ]
Filiz, Gulay [1 ]
Daniel, Paul M. [1 ]
Hollande, Frederic [1 ]
Dworkin, Sebastian [2 ]
Amiridis, Stephanie [3 ]
Kountouri, Nicole [4 ]
Ng, Wayne [4 ]
Morokoff, Andrew P. [4 ]
Mantamadiotis, Theo [1 ]
机构
[1] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia
[2] La Trobe Univ, Dept Physiol Anat & Microbiol, Melbourne, Vic, Australia
[3] Univ Melbourne, Dept Surg RMH, Melbourne, Vic, Australia
[4] Univ Melbourne, Dept Med RMH, Melbourne, Vic, Australia
关键词
CANCER; REVEALS; TRANSITIONS; METABOLISM; LANDSCAPE; SUBTYPES; STATES; BRAIN;
D O I
10.1371/journal.pone.0172791
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.
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页数:17
相关论文
共 39 条
[1]   CD44 IS THE PRINCIPAL CELL-SURFACE RECEPTOR FOR HYALURONATE [J].
ARUFFO, A ;
STAMENKOVIC, I ;
MELNICK, M ;
UNDERHILL, CB ;
SEED, B .
CELL, 1990, 61 (07) :1303-1313
[2]   CD133 Expression Is Not Synonymous to Immunoreactivity for AC133 and Fluctuates throughout the Cell Cycle in Glioma Stem-Like Cells [J].
Barrantes-Freer, Alonso ;
Renovanz, Mirjam ;
Eich, Marcus ;
Braukmann, Alina ;
Sprang, Bettina ;
Spirin, Pavel ;
Pardo, Luis A. ;
Giese, Alf ;
Kim, Ella L. .
PLOS ONE, 2015, 10 (06)
[3]   CD133+ and CD133- glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles [J].
Beier, Dagmar ;
Hau, Peter ;
Proescholdt, Martin ;
Lohmeier, Annette ;
Wischhusen, Joerg ;
Oefner, Peter J. ;
Aigner, Ludwig ;
Brawanski, Alexander ;
Bogdahn, Ulrich ;
Beier, Christoph P. .
CANCER RESEARCH, 2007, 67 (09) :4010-4015
[4]   Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma [J].
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 ;
Den Dunnen, Wilfred F. A. ;
Boddeke, Hendrikus W. G. M. ;
Phillips, Heidi S. ;
Nakano, Ichiro ;
Lang, Frederick F. ;
Colman, Howard ;
Sulman, Erik P. ;
Aldape, Kenneth .
CANCER CELL, 2013, 24 (03) :331-346
[5]   Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population [J].
Brat, DJ ;
Castellano-Sanchez, AA ;
Hunter, SB ;
Pecot, M ;
Cohen, C ;
Hammond, EH ;
Devi, SN ;
Kaur, B ;
Van Meir, EG .
CANCER RESEARCH, 2004, 64 (03) :920-927
[6]   The Somatic Genomic Landscape of Glioblastoma [J].
Brennan, Cameron W. ;
Verhaak, Roel G. W. ;
McKenna, Aaron ;
Campos, Benito ;
Noushmehr, Houtan ;
Salama, Sofie R. ;
Zheng, Siyuan ;
Chakravarty, Debyani ;
Sanborn, J. Zachary ;
Berman, Samuel H. ;
Beroukhim, Rameen ;
Bernard, Brady ;
Wu, Chang-Jiun ;
Genovese, Giannicola ;
Shmulevich, Ilya ;
Barnholtz-Sloan, Jill ;
Zou, Lihua ;
Vegesna, Rahulsimham ;
Shukla, Sachet A. ;
Ciriello, Giovanni ;
Yung, W. K. ;
Zhang, Wei ;
Sougnez, Carrie ;
Mikkelsen, Tom ;
Aldape, Kenneth ;
Bigner, Darell D. ;
Van Meir, Erwin G. ;
Prados, Michael ;
Sloan, Andrew ;
Black, Keith L. ;
Eschbacher, Jennifer ;
Finocchiaro, Gaetano ;
Friedman, William ;
Andrews, David W. ;
Guha, Abhijit ;
Iacocca, Mary ;
O'Neill, Brian P. ;
Foltz, Greg ;
Myers, Jerome ;
Weisenberger, Daniel J. ;
Penny, Robert ;
Kucherlapati, Raju ;
Perou, Charles M. ;
Hayes, D. Neil ;
Gibbs, Richard ;
Marra, Marco ;
Mills, Gordon B. ;
Lander, Eric ;
Spellman, Paul ;
Wilson, Richard .
CELL, 2013, 155 (02) :462-477
[7]   Coexpression analysis of CD133 and CD44 identifies Proneural and Mesenchymal subtypes of glioblastoma multiforme [J].
Brown, Daniel V. ;
Daniel, Paul M. ;
D'Abaco, Giovanna M. ;
Gogos, Andrew ;
Ng, Wayne ;
Morokoff, Andrew P. ;
Mantamadiotis, Theo .
ONCOTARGET, 2015, 6 (08) :6267-6280
[8]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[9]   Selective CREB-dependent cyclin expression mediated by the PI3K and MAPK pathways supports glioma cell proliferation [J].
Daniel, P. ;
Filiz, G. ;
Brown, D. V. ;
Hollande, F. ;
Gonzales, M. ;
D'Abaco, G. ;
Papalexis, N. ;
Phillips, W. A. ;
Malaterre, J. ;
Ramsay, R. G. ;
Mantamadiotis, T. .
ONCOGENESIS, 2014, 3 :e108-e108
[10]   Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma [J].
Galli, R ;
Binda, E ;
Orfanelli, U ;
Cipelletti, B ;
Gritti, A ;
De Vitis, S ;
Fiocco, R ;
Foroni, C ;
Dimeco, F ;
Vescovi, A .
CANCER RESEARCH, 2004, 64 (19) :7011-7021