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[Cancer Research 63, 5821-5828, September 15, 2003]
© 2003 American Association for Cancer Research

Regular Articles

Identification of a Cancer Stem Cell in Human Brain Tumors

Sheila K. Singh, Ian D. Clarke, Mizuhiko Terasaki, Victoria E. Bonn, Cynthia Hawkins, Jeremy Squire and Peter B. Dirks

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada [S. K. S., I. D. C., M. T., V. E. B., P. B. D.], and Program in Developmental Biology [S. K. S., I. D. C., M. T., V. E. B., P. B. D.], Division of Neurosurgery [S. K. S., P. B. D.], Department of Pediatric Laboratory Medicine [C. H.], and Department of Laboratory Medicine and Pathobiology [J. S.], University of Toronto, Toronto, Ontario M5G 1X8 Canada

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.




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