PMID- 17051156
OWN - NLM
STAT- MEDLINE
DCOM- 20070104
LR  - 20240109
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 444
IP  - 7120
DP  - 2006 Dec 7
TI  - Glioma stem cells promote radioresistance by preferential activation of the DNA 
      damage response.
PG  - 756-60
AB  - 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.
FAU - Bao, Shideng
AU  - Bao S
AD  - Department of Surgery, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Wu, Qiulian
AU  - Wu Q
FAU - McLendon, Roger E
AU  - McLendon RE
FAU - Hao, Yueling
AU  - Hao Y
FAU - Shi, Qing
AU  - Shi Q
FAU - Hjelmeland, Anita B
AU  - Hjelmeland AB
FAU - Dewhirst, Mark W
AU  - Dewhirst MW
FAU - Bigner, Darell D
AU  - Bigner DD
FAU - Rich, Jeremy N
AU  - Rich JN
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061018
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (AC133 Antigen)
RN  - 0 (Antigens, CD)
RN  - 0 (Glycoproteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
SB  - IM
CIN - Nature. 2006 Dec 7;444(7120):687-8. PMID: 17151644
MH  - AC133 Antigen
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Apoptosis
MH  - Brain Neoplasms/genetics/metabolism/*pathology
MH  - *DNA Damage/genetics
MH  - *DNA Repair
MH  - Glioblastoma/genetics/metabolism/pathology
MH  - Glioma/genetics/metabolism/*pathology
MH  - Glycoproteins/metabolism
MH  - Humans
MH  - Mice
MH  - Neoplastic Stem Cells/metabolism/*pathology/*radiation effects
MH  - Peptides/metabolism
MH  - *Radiation Tolerance
MH  - Stem Cell Transplantation
MH  - Transplantation, Heterologous
EDAT- 2006/10/20 09:00
MHDA- 2007/01/05 09:00
CRDT- 2006/10/20 09:00
PHST- 2006/06/01 00:00 [received]
PHST- 2006/09/07 00:00 [accepted]
PHST- 2006/10/20 09:00 [pubmed]
PHST- 2007/01/05 09:00 [medline]
PHST- 2006/10/20 09:00 [entrez]
AID - nature05236 [pii]
AID - 10.1038/nature05236 [doi]
PST - ppublish
SO  - Nature. 2006 Dec 7;444(7120):756-60. doi: 10.1038/nature05236. Epub 2006 Oct 18.