Cancerous Stem Cells Can Arise from Pediatric Brain Tumors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 25; pp. 15178 - 15183
• Main Authors: Hemmati, Houman D., Nakano, Ichiro, Lazareff, Jorge A., Masterman-Smith, Michael, Geschwind, Daniel H., Bronner-Fraser, Marianne, Kornblum, Harley I.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09-12-2003; National Acad Sciences
• Subjects: AC133 Antigen; Animals; Antigens, CD; Biological Sciences; Brain; Brain - pathology; Brain neoplasms; Brain Neoplasms - pathology; Bromodeoxyuridine - pharmacology; Cell Differentiation; Child; Coloring Agents - pharmacology; DNA-Binding Proteins - biosynthesis; Gene Expression Regulation, Neoplastic; Glioma; Glycoproteins - biosynthesis; HMGB Proteins; Humans; Immunohistochemistry; Infant; Medulloblastoma; Multipotent stem cells; Neoplasm Transplantation; Nerve Tissue Proteins - biosynthesis; Neural stem cells; Neuroglia; Neuroglia - pathology; Neurology; Neurons; Neurons - pathology; Nuclear Proteins - biosynthesis; Peptides; Phosphoric Monoester Hydrolases - biosynthesis; Progenitor cells; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA-Binding Proteins - biosynthesis; SOXB1 Transcription Factors; Stem cells; Stem Cells - pathology; Transcription Factors; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2036535100

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.