Telephone: 33-1-46-54-97-91, Fax: 33-1-46-54-97-02
Cancer Stem Cells
Article first published online: 21 MAR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 3, pages 440–451, March 2011
How to Cite
Silvestre, D. C., Pineda, J. R., Hoffschir, F., Studler, J.-M., Mouthon, M.-A., Pflumio, F., Junier, M.-P., Chneiweiss, H. and Boussin, F. D. (2011), Alternative Lengthening of Telomeres in Human Glioma Stem Cells. STEM CELLS, 29: 440–451. doi: 10.1002/stem.600
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: D.C.S.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; J.R.P. and F.H.: collection and assembly of data, data analysis and interpretation; J.-M.S. and M.-A.M.: collection and/or assembly of data; F.P., M.-P.J., and H.C.: provision of study material or patients and data interpretation; F.D.B.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.
First published online in STEM CELLSEXPRESS January 14, 2011.
- Issue published online: 21 MAR 2011
- Article first published online: 21 MAR 2011
- Accepted manuscript online: 14 JAN 2011 12:28PM EST
- Manuscript Accepted: 25 DEC 2010
- Manuscript Received: 31 AUG 2010
- CEA (Programme Plasticité et Instabilité des Génomes)
- DIM STEM-Pôle
- Tumor stem-like cells;
- Alternative lengthening of telomeres;
- Human glioma;
Cancer stem cells are increasingly recognized as major therapeutic targets. We report here the isolation of glioma stem cells (GSCs) maintaining telomere length through a telomerase-independent mechanism known as alternative lengthening of telomeres (ALTs). TG20 cells were isolated from a glioblastoma multiforme, which had the ALT phenotype. They have no detectable telomerase activity and extremely long and heterogeneous telomeres colocalizing with promyelocytic leukemia bodies. The cancer stem cell potential of TG20 cells was confirmed based on their expression of neural stem cell markers, their capacity of in vitro long-term proliferation and to form intracranial tumors in immune-deficient mice. Interestingly, we found that both in vitro and in vivo TG20 cells were significantly more resistant to ionizing radiation than GSCs with telomerase activity. Analysis of DNA damage foci, DNA double-strand breaks repair, and chromosome instability suggest that radiation resistance was related to interference of ALT pathway with DNA damage response. Therefore, our data show for the first time that the ALT pathway can confer to cancer stem cells the capacity to sustain long-term proliferation as telomerase activity and importantly may also affect treatment efficiency. TG20 cells are thus the first cellular model of GSCs displaying ALT and should prove to be useful for the development of specific treatment strategies. STEM CELLS 2011;29:440–451