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Title: Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion.
Authors: Hussein, D.
Punjaruk, W.
Storer, L. C.
Shaw, L.
Ottoman, R.
Peet, A.
Miller, S.
Bandopadhyay, G.
Heath, R.
Kumari, R.
Bowman, Karen Julia
Braker, P.
Rahman, R.
Jones, G. D.
Watson, S.
Lowe, J.
Kerr, I. D.
Grundy, R. G.
Coyle, B.
First Published: 25-Oct-2010
Publisher: Oxford University Press (OUP)
Citation: Neuro-Oncology, 2011, 13 (1), pp. 70-83
Abstract: Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3-4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents.
DOI Link: 10.1093/neuonc/noq144
ISSN: 1522-8517
eISSN: 1523-5866
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author(s) 2010. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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