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, Harley I. Kornblum

Research output: Contribution to journalArticlepeer-review

1597 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)15178-15183
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number25
DOIs
StatePublished - 9 Dec 2003
Externally publishedYes

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