PMID- 15549107
OWN - NLM
STAT- MEDLINE
DCOM- 20041221
LR  - 20230131
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 432
IP  - 7015
DP  - 2004 Nov 18
TI  - Identification of human brain tumour initiating cells.
PG  - 396-401
AB  - The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are 
      maintained exclusively by a rare fraction of cells with stem cell properties. 
      Although the existence of CSCs in human leukaemia is established, little evidence 
      exists for CSCs in solid tumours, except for breast cancer. Recently, we 
      prospectively isolated a CD133+ cell subpopulation from human brain tumours that 
      exhibited stem cell properties in vitro. However, the true measures of CSCs are 
      their capacity for self renewal and exact recapitulation of the original tumour. 
      Here we report the development of a xenograft assay that identified human brain 
      tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain 
      tumour fraction contains cells that are capable of tumour initiation in NOD-SCID 
      (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of 
      as few as 100 CD133+ cells produced a tumour that could be serially transplanted 
      and was a phenocopy of the patient's original tumour, whereas injection of 10(5) 
      CD133- cells engrafted but did not cause a tumour. Thus, the identification of 
      brain tumour initiating cells provides insights into human brain tumour 
      pathogenesis, giving 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.
FAU - Singh, Sheila K
AU  - Singh SK
AD  - The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick 
      Children and University of Toronto, 555 University Avenue, Toronto, M5G 1X8, 
      Canada.
FAU - Hawkins, Cynthia
AU  - Hawkins C
FAU - Clarke, Ian D
AU  - Clarke ID
FAU - Squire, Jeremy A
AU  - Squire JA
FAU - Bayani, Jane
AU  - Bayani J
FAU - Hide, Takuichiro
AU  - Hide T
FAU - Henkelman, R Mark
AU  - Henkelman RM
FAU - Cusimano, Michael D
AU  - Cusimano MD
FAU - Dirks, Peter B
AU  - Dirks PB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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. 2004 Nov 18;432(7015):281-2. PMID: 15549078
MH  - AC133 Antigen
MH  - Animals
MH  - Antigens, CD
MH  - Brain/metabolism/pathology
MH  - Brain Neoplasms/genetics/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Cell Separation
MH  - Cell Transplantation
MH  - Glycoproteins/analysis/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Medulloblastoma/genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Models, Biological
MH  - Neoplasm Transplantation
MH  - Peptides/analysis/metabolism
MH  - Stem Cells/metabolism/*pathology
EDAT- 2004/11/19 09:00
MHDA- 2004/12/22 09:00
CRDT- 2004/11/19 09:00
PHST- 2004/09/07 00:00 [received]
PHST- 2004/10/22 00:00 [accepted]
PHST- 2004/11/19 09:00 [pubmed]
PHST- 2004/12/22 09:00 [medline]
PHST- 2004/11/19 09:00 [entrez]
AID - nature03128 [pii]
AID - 10.1038/nature03128 [doi]
PST - ppublish
SO  - Nature. 2004 Nov 18;432(7015):396-401. doi: 10.1038/nature03128.