Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma
Rossella Galli,Elena Binda,Ugo Orfanelli,Barbara Cipelletti,Angela Gritti,Simona De Vitis,Roberta Fiocco,Chiara Foroni,Francesco DiMeco,Angelo L. Vescovi +9 more
TLDR
It is reported that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells.Abstract:
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.read more
Citations
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Identification of human brain tumour initiating cells
Sheila K. Singh,Cynthia Hawkins,Ian D. Clarke,Jeremy A. Squire,Jane Bayani,Takuichiro Hide,R. Mark Henkelman,Michael D. Cusimano,Peter B. Dirks +8 more
TL;DR: The development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo gives strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
Journal ArticleDOI
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
Shideng Bao,Qiulian Wu,Roger E. McLendon,Yueling Hao,Qing Ming Shi,Anita B. Hjelmeland,Mark W. Dewhirst,Darell D. Bigner,Jeremy N. Rich +8 more
TL;DR: This work shows that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity, and suggests that CD133-positive tumour cells could be the source of tumour recurrence after radiation.
Journal ArticleDOI
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
TL;DR: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM) and proposed a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes as discussed by the authors.
Journal ArticleDOI
Cancer stem cells in solid tumours: accumulating evidence and unresolved questions
TL;DR: The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours.
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Journal Article
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TL;DR: 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 is reported.
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