Skip to main content
Journal cover image

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.

Publication ,  Journal Article
Bao, S; Wu, Q; McLendon, RE; Hao, Y; Shi, Q; Hjelmeland, AB; Dewhirst, MW; Bigner, DD; Rich, JN
Published in: Nature
December 7, 2006

Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying tumour radioresistance have remained elusive. Here we show that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of tumour cells expressing CD133 (Prominin-1), a marker for both neural stem cells and brain cancer stem cells, is enriched after radiation in gliomas. In both cell culture and the brains of immunocompromised mice, CD133-expressing glioma cells survive ionizing radiation in increased proportions relative to most tumour cells, which lack CD133. CD133-expressing tumour cells isolated from both human glioma xenografts and primary patient glioblastoma specimens preferentially activate the DNA damage checkpoint in response to radiation, and repair radiation-induced DNA damage more effectively than CD133-negative tumour cells. In addition, the radioresistance of CD133-positive glioma stem cells can be reversed with a specific inhibitor of the Chk1 and Chk2 checkpoint kinases. Our results suggest that CD133-positive tumour cells represent the cellular population that confers glioma radioresistance and could be the source of tumour recurrence after radiation. Targeting DNA damage checkpoint response in cancer stem cells may overcome this radioresistance and provide a therapeutic model for malignant brain cancers.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

December 7, 2006

Volume

444

Issue

7120

Start / End Page

756 / 760

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Stem Cell Transplantation
  • Radiation Tolerance
  • Peptides
  • Neoplastic Stem Cells
  • Mice
  • Humans
  • Glycoproteins
  • Glioma
  • Glioblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., … Rich, J. N. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature, 444(7120), 756–760. https://doi.org/10.1038/nature05236
Bao, Shideng, Qiulian Wu, Roger E. McLendon, Yueling Hao, Qing Shi, Anita B. Hjelmeland, Mark W. Dewhirst, Darell D. Bigner, and Jeremy N. Rich. “Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.Nature 444, no. 7120 (December 7, 2006): 756–60. https://doi.org/10.1038/nature05236.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756–60.
Bao, Shideng, et al. “Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.Nature, vol. 444, no. 7120, Dec. 2006, pp. 756–60. Pubmed, doi:10.1038/nature05236.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756–760.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

December 7, 2006

Volume

444

Issue

7120

Start / End Page

756 / 760

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Stem Cell Transplantation
  • Radiation Tolerance
  • Peptides
  • Neoplastic Stem Cells
  • Mice
  • Humans
  • Glycoproteins
  • Glioma
  • Glioblastoma