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[Cancer Research 63, 5821-5828, September 15, 2003]
© 2003 American Association for Cancer Research

Regular Articles

Identification of a Cancer Stem Cell in Human Brain Tumors

Sheila K. Singh, Ian D. Clarke, Mizuhiko Terasaki, Victoria E. Bonn, Cynthia Hawkins, Jeremy Squire and Peter B. Dirks

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada [S. K. S., I. D. C., M. T., V. E. B., P. B. D.], and Program in Developmental Biology [S. K. S., I. D. C., M. T., V. E. B., P. B. D.], Division of Neurosurgery [S. K. S., P. B. D.], Department of Pediatric Laboratory Medicine [C. H.], and Department of Laboratory Medicine and Pathobiology [J. S.], University of Toronto, Toronto, Ontario M5G 1X8 Canada

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.




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Gut, April 1, 2008; 57(4): 538 - 548.
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 Cancer Res.Home page
K. Engelmann, H. Shen, and O. J. Finn
MCF7 Side Population Cells with Characteristics of Cancer Stem/Progenitor Cells Express the Tumor Antigen MUC1
Cancer Res., April 1, 2008; 68(7): 2419 - 2426.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
A. G. Gilg, S. L. Tye, L. B. Tolliver, W. G. Wheeler, R. P. Visconti, J. D. Duncan, F. V. Kostova, L. N. Bolds, B. P. Toole, and B. L. Maria
Targeting Hyaluronan Interactions in Malignant Gliomas and Their Drug-Resistant Multipotent Progenitors
Clin. Cancer Res., March 15, 2008; 14(6): 1804 - 1813.
[Abstract] [Full Text] [PDF]

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 Vet PatholHome page
M. M. Bera, D. N. R. Veeramachaneni, and K. Pandher
Characterization of a Biphasic Neoplasm in a Madagascar Tree Boa (Sanzinia madagascariensis)
Vet. Pathol., March 1, 2008; 45(2): 259 - 263.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
U. D. Lichtenauer, I. Shapiro, K. Geiger, M. Quinkler, M. Fassnacht, R. Nitschke, K.-D. Ruckauer, and F. Beuschlein
Side Population Does Not Define Stem Cell-Like Cancer Cells in the Adrenocortical Carcinoma Cell Line NCI h295R
Endocrinology, March 1, 2008; 149(3): 1314 - 1322.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
D. Hambardzumyan, O. J. Becher, M. K. Rosenblum, P. P. Pandolfi, K. Manova-Todorova, and E. C. Holland
PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo
Genes & Dev., February 15, 2008; 22(4): 436 - 448.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Liu, C. Ginestier, E. Charafe-Jauffret, H. Foco, C. G. Kleer, S. D. Merajver, G. Dontu, and M. S. Wicha
BRCA1 regulates human mammary stem/progenitor cell fate
PNAS, February 5, 2008; 105(5): 1680 - 1685.
[Abstract] [Full Text] [PDF]

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 Phil Trans R Soc BHome page
P. B Dirks
Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells
Phil Trans R Soc B, January 12, 2008; 363(1489): 139 - 152.
[Abstract] [Full Text] [PDF]

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 Phil Trans R Soc BHome page
K. J.L Fernandes, J. G Toma, and F. D Miller
Multipotent skin-derived precursors: adult neural crest-related precursors with therapeutic potential
Phil Trans R Soc B, January 12, 2008; 363(1489): 185 - 198.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. M. Hansford, A. E. McKee, L. Zhang, R. E. George, J. T. Gerstle, P. S. Thorner, K. M. Smith, A. T. Look, H. Yeger, F. D. Miller, et al.
Neuroblastoma Cells Isolated from Bone Marrow Metastases Contain a Naturally Enriched Tumor-Initiating Cell
Cancer Res., December 1, 2007; 67(23): 11234 - 11243.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al.
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Genes & Dev., November 1, 2007; 21(21): 2683 - 2710.
[Abstract] [Full Text] [PDF]

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 BloodHome page
L. Nilsson, P. Eden, E. Olsson, R. Mansson, I. Astrand-Grundstrom, B. Strombeck, K. Theilgaard-Monch, K. Anderson, R. Hast, E. Hellstrom-Lindberg, et al.
The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes
Blood, October 15, 2007; 110(8): 3005 - 3014.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
R. P. Hill and R. Perris
"Destemming" Cancer Stem Cells
J Natl Cancer Inst, October 3, 2007; 99(19): 1435 - 1440.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. N. Rich
Cancer Stem Cells in Radiation Resistance
Cancer Res., October 1, 2007; 67(19): 8980 - 8984.
[Abstract] [Full Text] [PDF]

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 Ann OncolHome page
M. Mimeault and S. K. Batra
Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies
Ann. Onc., October 1, 2007; 18(10): 1605 - 1619.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. Faber and S. A. Armstrong
Mixed Lineage Leukemia Translocations and a Leukemia Stem Cell Program
Cancer Res., September 15, 2007; 67(18): 8425 - 8428.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. C. Liu, T. Deng, R. S. Lehal, J. Kim, and E. Zacksenhaus
Identification of Tumorsphere- and Tumor-Initiating Cells in HER2/Neu-Induced Mammary Tumors
Cancer Res., September 15, 2007; 67(18): 8671 - 8681.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. Wu, Q. Wei, V. Utomo, P. Nadesan, H. Whetstone, R. Kandel, J. S. Wunder, and B. A. Alman
Side Population Cells Isolated from Mesenchymal Neoplasms Have Tumor Initiating Potential
Cancer Res., September 1, 2007; 67(17): 8216 - 8222.
[Abstract] [Full Text] [PDF]

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 GlycobiologyHome page
M. Yanagisawa and R. K Yu
The expression and functions of glycoconjugates in neural stem cells
Glycobiology, July 1, 2007; 17(7): 57R - 74R.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. V. Pfenninger, T. Roschupkina, F. Hertwig, D. Kottwitz, E. Englund, J. Bengzon, S. E. Jacobsen, and U. A. Nuber
CD133 Is Not Present on Neurogenic Astrocytes in the Adult Subventricular Zone, but on Embryonic Neural Stem Cells, Ependymal Cells, and Glioblastoma Cells
Cancer Res., June 15, 2007; 67(12): 5727 - 5736.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Beier, P. Hau, M. Proescholdt, A. Lohmeier, J. Wischhusen, P. J. Oefner, L. Aigner, A. Brawanski, U. Bogdahn, and C. P. Beier
CD133+ and CD133- Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles
Cancer Res., May 1, 2007; 67(9): 4010 - 4015.
[Abstract] [Full Text] [PDF]

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 Hum ReprodHome page
K. Kato, M. Yoshimoto, K. Kato, S. Adachi, A. Yamayoshi, T. Arima, K. Asanoma, S. Kyo, T. Nakahata, and N. Wake
Characterization of side-population cells in human normal endometrium
Hum. Reprod., May 1, 2007; 22(5): 1214 - 1223.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. Folkins, S. Man, P. Xu, Y. Shaked, D. J. Hicklin, and R. S. Kerbel
Anticancer Therapies Combining Antiangiogenic and Tumor Cell Cytotoxic Effects Reduce the Tumor Stem-Like Cell Fraction in Glioma Xenograft Tumors
Cancer Res., April 15, 2007; 67(8): 3560 - 3564.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
X. Zheng, G. Shen, X. Yang, and W. Liu
Most C6 Cells Are Cancer Stem Cells: Evidence from Clonal and Population Analyses
Cancer Res., April 15, 2007; 67(8): 3691 - 3697.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. Wang, L.-P. Guo, L.-Z. Chen, Y.-X. Zeng, and S. H. Lu
Identification of Cancer Stem Cell-Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Cancer Res., April 15, 2007; 67(8): 3716 - 3724.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. Foroni, R. Galli, B. Cipelletti, A. Caumo, S. Alberti, R. Fiocco, and A. Vescovi
Resilience to Transformation and Inherent Genetic and Functional Stability of Adult Neural Stem Cells Ex vivo
Cancer Res., April 15, 2007; 67(8): 3725 - 3733.
[Abstract] [Full Text] [PDF]

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 JCOHome page
D. Faury, A. Nantel, S. E. Dunn, M.-C. Guiot, T. Haque, P. Hauser, M. Garami, L. Bognar, Z. Hanzely, P. P. Liberski, et al.
Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors
J. Clin. Oncol., April 1, 2007; 25(10): 1196 - 1208.
[Abstract] [Full Text] [PDF]


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