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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.
© 2003 American Association for Cancer Research
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