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[Cancer Research 64, 7011-7021, October 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma

Rossella Galli1, Elena Binda1, Ugo Orfanelli1, Barbara Cipelletti1, Angela Gritti1, Simona De Vitis2, Roberta Fiocco1, Chiara Foroni1, Francesco Dimeco3,4 and Angelo Vescovi1,5

1 Stem Cell Research Institute and 2 Laboratory of Molecular Diagnostics, H. S. Raffaele, Milan, Italy; 3 National Neurological Institute "C. Besta," Milan, Italy; 4 Department of Neurological Surgery, Johns Hopkins Medical School, Baltimore, Maryland; and 5 Department of Biological Sciences and Biotechnology, University of Milano-Bicocca, Milan, Italy

Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipotent (astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly, these cells can act as tumor-founding cells down to the clonal level and can establish tumors that closely resemble the main histologic, cytologic, and architectural features of the human disease, even when challenged through serial transplantation. Thus, cells possessing all of the characteristics expected from tumor neural stem cells seem to be involved in the growth and recurrence of adult human glioblastomas multiforme.




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 CarcinogenesisHome page
J.M. Ordway, J.A. Bedell, R.W. Citek, A. Nunberg, A. Garrido, R. Kendall, J.R. Stevens, D. Cao, R.W. Doerge, Y. Korshunova, et al.
Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets
Carcinogenesis, December 1, 2006; 27(12): 2409 - 2423.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
N. Redjal, J. A. Chan, R. A. Segal, and A. L. Kung
CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas.
Clin. Cancer Res., November 15, 2006; 12(22): 6765 - 6771.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Horvath, B. Zhang, M. Carlson, K. V. Lu, S. Zhu, R. M. Felciano, M. F. Laurance, W. Zhao, S. Qi, Z. Chen, et al.
Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target
PNAS, November 14, 2006; 103(46): 17402 - 17407.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
C. T. Jordan, M. L. Guzman, and M. Noble
Cancer stem cells.
N. Engl. J. Med., September 21, 2006; 355(12): 1253 - 1261.
[Full Text] [PDF]

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 Cancer Res.Home page
L. Balenci, I. D. Clarke, P. B. Dirks, N. Assard, F. Ducray, A. Jouvet, M.-F. Belin, J. Honnorat, and J. Baudier
IQGAP1 Protein Specifies Amplifying Cancer Cells in Glioblastoma Multiforme.
Cancer Res., September 15, 2006; 66(18): 9074 - 9082.
[Abstract] [Full Text] [PDF]

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 Mol Cancer ResHome page
C.-L. Tso, P. Shintaku, J. Chen, Q. Liu, J. Liu, Z. Chen, K. Yoshimoto, P. S. Mischel, T. F. Cloughesy, L. M. Liau, et al.
Primary Glioblastomas Express Mesenchymal Stem-Like Properties
Mol. Cancer Res., September 1, 2006; 4(9): 607 - 619.
[Abstract] [Full Text] [PDF]

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 Molecular Cancer TherapeuticsHome page
N. Auger, J. Thillet, K. Wanherdrick, A. Idbaih, M.-E. Legrier, B. Dutrillaux, M. Sanson, and M.-F. Poupon
Genetic alterations associated with acquired temozolomide resistance in SNB-19, a human glioma cell line.
Mol. Cancer Ther., September 1, 2006; 5(9): 2182 - 2192.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. Bao, Q. Wu, S. Sathornsumetee, Y. Hao, Z. Li, A. B. Hjelmeland, Q. Shi, R. E. McLendon, D. D. Bigner, and J. N. Rich
Stem Cell-like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor
Cancer Res., August 15, 2006; 66(16): 7843 - 7848.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
X. Fan, W. Matsui, L. Khaki, D. Stearns, J. Chun, Y.-M. Li, and C. G. Eberhart
Notch Pathway Inhibition Depletes Stem-like Cells and Blocks Engraftment in Embryonal Brain Tumors.
Cancer Res., August 1, 2006; 66(15): 7445 - 7452.
[Abstract] [Full Text] [PDF]

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 J. Neurol. Neurosurg. PsychiatryHome page
J. Olesen, M. G Baker, T. Freund, M. di Luca, J. Mendlewicz, I. Ragan, and M. Westphal
Consensus document on European brain research
J. Neurol. Neurosurg. Psychiatry, August 1, 2006; 77(suppl_1): i1 - i49.
[Abstract] [Full Text] [PDF]

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 Sci Aging Knowl EnvironHome page
J. Fuller
Stem cell aging and cancer.
Sci. Aging Knowl. Environ., May 15, 2006; 2006(9): pe12 - pe12.
[Abstract] [Full Text]

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 JCOHome page
D. A. Reardon, J. N. Rich, H. S. Friedman, and D. D. Bigner
Recent Advances in the Treatment of Malignant Astrocytoma
J. Clin. Oncol., March 10, 2006; 24(8): 1253 - 1265.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. Groszer, R. Erickson, D. D. Scripture-Adams, J. D. Dougherty, J. Le Belle, J. A. Zack, D. H. Geschwind, X. Liu, H. I. Kornblum, and H. Wu
PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry
PNAS, January 3, 2006; 103(1): 111 - 116.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. D. Dougherty, A. D. R. Garcia, I. Nakano, M. Livingstone, B. Norris, R. Polakiewicz, E. M. Wexler, M. V. Sofroniew, H. I. Kornblum, and D. H. Geschwind
PBK/TOPK, a Proliferating Neural Progenitor-Specific Mitogen-Activated Protein Kinase Kinase
J. Neurosci., November 16, 2005; 25(46): 10773 - 10785.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
H. S. Taylor and X. Fei
Emx2 Regulates Mammalian Reproduction by Altering Endometrial Cell Proliferation
Mol. Endocrinol., November 1, 2005; 19(11): 2839 - 2846.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Fang, T. K. Nguyen, K. Leishear, R. Finko, A. N. Kulp, S. Hotz, P. A. Van Belle, X. Xu, D. E. Elder, and M. Herlyn
A Tumorigenic Subpopulation with Stem Cell Properties in Melanomas
Cancer Res., October 15, 2005; 65(20): 9328 - 9337.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
N. Sanai, A. Alvarez-Buylla, and M. S. Berger
Neural Stem Cells and the Origin of Gliomas
N. Engl. J. Med., August 25, 2005; 353(8): 811 - 822.
[Full Text] [PDF]

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 Clin. Cancer Res.Home page
S.-K. Kim, T. G. Cargioli, M. Machluf, W. Yang, Y. Sun, R. Al-Hashem, S. U. Kim, P. M. Black, and R. S. Carroll
PEX-Producing Human Neural Stem Cells Inhibit Tumor Growth in a Mouse Glioma Model
Clin. Cancer Res., August 15, 2005; 11(16): 5965 - 5970.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. Patrawala, T. Calhoun, R. Schneider-Broussard, J. Zhou, K. Claypool, and D. G. Tang
Side Population Is Enriched in Tumorigenic, Stem-Like Cancer Cells, whereas ABCG2+ and ABCG2- Cancer Cells Are Similarly Tumorigenic
Cancer Res., July 15, 2005; 65(14): 6207 - 6219.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Ponti, A. Costa, N. Zaffaroni, G. Pratesi, G. Petrangolini, D. Coradini, S. Pilotti, M. A. Pierotti, and M. G. Daidone
Isolation and In vitro Propagation of Tumorigenic Breast Cancer Cells with Stem/Progenitor Cell Properties
Cancer Res., July 1, 2005; 65(13): 5506 - 5511.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
B. Dasgupta and D. H. Gutmann
Neurofibromin Regulates Neural Stem Cell Proliferation, Survival, and Astroglial Differentiation In Vitro and In Vivo
J. Neurosci., June 8, 2005; 25(23): 5584 - 5594.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. A. Bapat, A. M. Mali, C. B. Koppikar, and N. K. Kurrey
Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian Cancer
Cancer Res., April 15, 2005; 65(8): 3025 - 3029.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
R. Glass, M. Synowitz, G. Kronenberg, J.-H. Walzlein, D. S. Markovic, L.-P. Wang, D. Gast, J. Kiwit, G. Kempermann, and H. Kettenmann
Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival
J. Neurosci., March 9, 2005; 25(10): 2637 - 2646.
[Abstract] [Full Text] [PDF]


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