Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.
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 in vivo malignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cells in vitro and in vivo. 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.
Kondo
Toru
T
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. tk294@cam.ac.uk
Setoguchi
Takao
T
Taga
Tetsuya
T
D000818:Animals; D045744:Cell Line, Tumor; D002469:Cell Separation; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000145:classification / Q000187:drug effects / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay
D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2