Cancerous stem cells can arise from pediatric brain tumors.

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.
Authors	Houman D Hemmati, Ichiro Nakano, Jorge A Lazareff, Michael Masterman-Smith, Daniel H Geschwind, Marianne Bronner-Fraser, Harley I Kornblum
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 25 Pg. 15178-83 (Dec 09 2003) ISSN: 0027-8424 [Print] United States
PMID	14645703 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	AC133 Antigen Antigens, CD Coloring Agents DNA-Binding Proteins Glycoproteins HMGB Proteins MSI1 protein, human Msi1 protein, rat Nerve Tissue Proteins Nuclear Proteins PROM1 protein, human Peptides Prom1 protein, rat RNA-Binding Proteins SOX2 protein, human SOXB1 Transcription Factors Sox2 protein, rat Transcription Factors Phosphoric Monoester Hydrolases phosphoserine phosphatase Bromodeoxyuridine
Topics	AC133 Antigen Animals Antigens, CD Brain (pathology) Brain Neoplasms (pathology) Bromodeoxyuridine (pharmacology) Cell Differentiation Child Coloring Agents (pharmacology) DNA-Binding Proteins (biosynthesis) Gene Expression Regulation, Neoplastic Glycoproteins (biosynthesis) HMGB Proteins Humans Immunohistochemistry Infant Neoplasm Transplantation Nerve Tissue Proteins (biosynthesis) Neuroglia (pathology) Neurons (pathology) Nuclear Proteins (biosynthesis) Peptides Phosphoric Monoester Hydrolases (biosynthesis) RNA-Binding Proteins (biosynthesis) Rats Reverse Transcriptase Polymerase Chain Reaction SOXB1 Transcription Factors Stem Cells (pathology) Transcription Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!