Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line

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  • Toru Kondo
    Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;Centre for Brain Repair, University of Cambridge, E. D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, United Kingdom; and Department of Orthopaedic Surgery, Kagoshima Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
  • Takao Setoguchi
    Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;Centre for Brain Repair, University of Cambridge, E. D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, United Kingdom; and Department of Orthopaedic Surgery, Kagoshima Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
  • Tetsuya Taga
    Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;Centre for Brain Repair, University of Cambridge, E. D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, United Kingdom; and Department of Orthopaedic Surgery, Kagoshima Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan

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<jats:p> Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Paradoxically, however, some cancers seem to contain stem-like cells (cancer stem cells). To help resolve this paradox, we investigated whether established malignant cell lines, which have been maintained for years in culture, contain a subpopulation of stem cells. In this article, we show that many cancer cell lines contain a small side population (SP), which, in many normal tissues, is thought to contain the stem cells of the tissue. We demonstrate that in the absence of serum the combination of basic fibroblast growth factor and platelet-derived growth factor maintains SP cells in the C6 glioma cell line. Moreover, we show that C6 SP cells, but not non-SP cells, can generate both SP and non-SP cells in culture and are largely responsible for the <jats:italic>in vivo</jats:italic> malignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cells <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> . We propose that many cancer cell lines contain a minor subpopulation of stem cells that is enriched in an SP, can be maintained indefinitely in culture, and is crucial for their malignancy. </jats:p>

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