Identification of human brain tumour initiating cells (original) (raw)

Nature volume 432, pages 396–401 (2004)Cite this article

Abstract

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties1,2. Although the existence of CSCs in human leukaemia is established3,4, little evidence exists for CSCs in solid tumours, except for breast cancer5. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro6. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour1,2,7. 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 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 tumours5, and establishes a previously unidentified cellular target for more effective cancer therapies.

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Acknowledgements

We thank M. Borden, J. Ma, I. Diplock, M. Ho and C. Gibson for technical assistance, and we are grateful to V. Bonn, L. Davidson, N. Lifshitz and J. Chen of the Mouse Imaging Centre for help with neuroimaging. We thank J. Dick for discussions. S. Singh was supported by a a Terry Fox Foundation fellowship from the Canadian Cancer Society, the Neurosurgical Research and Education Foundation and the American Brain Tumor Association. This work was supported by the Canadian Cancer Society, the Canadian Institutes of Health Research, the Foundation of The Hospital for Sick Children, BrainChild and the Jack Baker and Jessica Durigon family funds.

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Authors and Affiliations

  1. The Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Canada
    Sheila K. Singh, Cynthia Hawkins, Ian D. Clarke, Takuichiro Hide & Peter B. Dirks
  2. Program in Developmental Biology, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Canada
    Sheila K. Singh, Ian D. Clarke, Takuichiro Hide & Peter B. Dirks
  3. Division of Neurosurgery, University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Canada
    Sheila K. Singh, Michael D. Cusimano & Peter B. Dirks
  4. Department of Pediatric Laboratory Medicine, University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Canada
    Cynthia Hawkins
  5. Integrative Biology Program, The Hospital for Sick Children and University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Canada
    R. Mark Henkelman
  6. Ontario Cancer Institute and University of Toronto, 610 University Avenue, M5G 2M9, Toronto, Canada
    Jeremy A. Squire & Jane Bayani
  7. Division of Neurosurgery, St Michael's Hospital and University of Toronto, 30 Bond Street, M5B 1W8, Toronto, Canada
    Michael D. Cusimano

Authors

  1. Sheila K. Singh
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  2. Cynthia Hawkins
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  3. Ian D. Clarke
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  4. Jeremy A. Squire
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  5. Jane Bayani
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  6. Takuichiro Hide
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  7. R. Mark Henkelman
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  8. Michael D. Cusimano
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  9. Peter B. Dirks
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Correspondence toPeter B. Dirks.

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Singh, S., Hawkins, C., Clarke, I. et al. Identification of human brain tumour initiating cells.Nature 432, 396–401 (2004). https://doi.org/10.1038/nature03128

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