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Cancerous
stem cells can arise from pediatric brain tumors
Houman D. Hemmati, Ichiro
Nakano, Jorge A. Lazareff, Michael Masterman-Smith, Daniel H.
Geschwind, Marianne Bronner-Fraser
and Harley I. Kornblum
Division of Biology 139-74, California Institute of
Technology, Pasadena, CA 91125 [H.D.H., M.B.-F.]; and Department of Molecular and Medical
Pharmacology [I.N., H.I.K.], Division of Neurosurgery [J.A.L., M.M.-S.], and Departments of
Pediatrics [J.A.L., H.I.K.] and Neurology [D.H.G.], David Geffen School of Medicine, University of
California, Los Angeles, CA 90095.
[HIK] To whom correspondence should be addressed
at: Room 1126 CIMI, 700 Westwood Plaza, Los Angeles, CA 90095. E-mail:
hkornblum@mednet.ucla.edu.
Communicated by Michael E. Phelps, University of California School of
Medicine, Los Angeles, CA, October 8, 2003 (received for review June 20, 2003)
Pediatric brain tumors are significant causes of morbidity and mortality.
It has been hypothesized that they derive from self-renewing
multipotent neural stem cells.
Here, we tested whether different pediatric brain
tumors, including medulloblastomas and gliomas, contain cells with
properties similar to neural stem cells.
We find that tumor-derived progenitors form neurospheres that
can be passaged at clonal density and are able to self-renew.
Under conditions promoting differentiation, individual cells
are multipotent, giving rise to both neurons and glia, in proportions
that reflect the tumor of origin.
Unlike normal neural stem cells, however,
tumor-derived progenitors have an unusual capacity to proliferate and
sometimes differentiate into abnormal cells with multiple
differentiation markers.
Gene expression analysis reveals that both whole
tumors and tumor-derived neurospheres express many genes
characteristic of neural and other stem cells, including CD133, Sox2,
musashi-1, bmi-1, maternal embryonic leucine zipper kinase,
and phosphoserine phosphatase, with variation from tumor to
tumor.
After grafting to neonatal rat brains, tumor-derived
neurosphere cells migrate, produce neurons and glia, and continue to
proliferate for more than 4 weeks.
The results show that pediatric brain tumors contain
neural stem-like cells with altered characteristics that may
contribute to tumorigenesis.
This finding may have important implications for treatment by
means of specific targeting of stem-like cells within brain tumors.
Copyright © 2003 by the
National Academy of Sciences
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