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| Identification of human brain tumour initiating cells |
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| Author(s): Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB |
| Source: NATURE Volume: 432 Issue: 7015 Pages: 396-401 Published: NOV 18 2004 |
| Times Cited: 1,100 References: 29 |
| Abstract: The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties(1,2). Although the existence of CSCs in human leukaemia is established(3,4), little evidence exists for CSCs in solid tumours, except for breast cancer(5). Recently, we prospectively isolated a CD133(+) cell subpopulation from human brain tumours that exhibited stem cell properties in vitro(6). However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour(1,2,7). 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(5), and establishes a previously unidentified cellular target for more effective cancer therapies. |
| Document Type: Article |
| Language: English |
| Reprint Address: Dirks, PB (reprint author), Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt brain Tumor Res Ctr, 555 Univ Ave, Toronto, ON M5G 1X8 Canada |
Addresses:
1. Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt brain Tumor Res Ctr, Toronto, ON M5G 1X8 Canada
2. Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8 Canada
3. Univ Toronto, Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8 Canada
4. Univ Toronto, Hosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8 Canada
5. Univ Toronto, Hosp Sick Children, Integrat Biol Program, Toronto, ON M5G 1X8 Canada
6. Ontario Canc Inst, Toronto, ON M5G 2M9 Canada
7. Univ Toronto, Toronto, ON M5G 2M9 Canada
8. St Michaels Hosp, Div Neurosurg, Toronto, ON M5B 1W8 Canada
9. Univ Toronto, Toronto, ON M5B 1W8 Canada |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 871UX |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature03128 |
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