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- Title
Identification of human brain tumour initiating cells.
- Authors
Singh, Sheila K.; Hawkins, Cynthia; Clarke, Ian D.; Squire, Jeremy A.; Bayani, Jane; Hide, Takuichiro; Henkelman, R. Mark; Cusimano, Michael D.; Dirks, Peter B.
- Abstract
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 105 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.
- Subjects
STEM cells; BRAIN tumors; CANCER treatment; TRANSPLANTATION of organs, tissues, etc.; PEOPLE with diabetes; XENOGRAFTS
- Publication
Nature, 2004, Vol 432, Issue 7015, p396
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature03128