DOI: 10.1073/pnas.0307618100. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line

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

10.1073/pnas.0307618100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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.

Bibliography

Kondo, T., Setoguchi, T., & Taga, T. (2004). Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proceedings of the National Academy of Sciences, 101(3), 781â786.

Authors 3

Toru Kondo (first)
Takao Setoguchi (additional)
Tetsuya Taga (additional)

References 37 Referenced 779

10.1016/0014-4827(65)90211-9
Poste, G. & Greig, R. (1982) Invasion Metastasis 2, 137–176.6765249 / Invasion Metastasis (1982)
10.1038/bjc.1983.96
Sell, S. & Pierce, G. B. (1994) Lab. Invest 70, 6–22.8302019 / Lab. Invest (1994)
10.1038/35102167
10.1016/S1470-2045(02)00820-3
10.1007/s004010050730
10.1046/j.1365-2990.1998.00132.x
10.1093/jnen/61.4.307
10.1101/gad.903001
10.1097/00019052-200112000-00002
10.1016/S0092-8674(00)80783-7
10.1126/science.289.5485.1754
10.1073/pnas.230146497
10.1016/S0361-9230(01)00777-8
10.1083/jcb.200210110
10.1038/nm837
10.1038/nrc706
10.1084/jem.183.4.1797
10.1073/pnas.95.26.15665
10.1038/nm0901-1028
10.1073/pnas.192276999
10.1038/333560a0
10.1038/333562a0
10.1016/0092-8674(88)90392-3
10.1126/science.7682010
10.1002/neu.480250705
10.1523/JNEUROSCI.19-11-04462.1999
10.1002/stem.200011
10.1002/1097-0320(20000701)40:3<245::AID-CYTO10>3.0.CO;2-5
Makino, S. (1956) Ann. N.Y. Acad. Sci. 63, 813–883. / Ann. N.Y. Acad. Sci. (1956)
Kleinsmith, L. J. & Pierce, G. B. (1964) Cancer Res. 24, 1544–1552.14234000 / Cancer Res. (1964)
Gale, R. P. & Butturini, A. (1992) Leukemia 6, 80–85.1548943 / Leukemia (1992)
10.1182/blood.V98.4.1166
10.1073/pnas.0530291100
10.1016/S0093-7754(01)90279-9
Aoki, T., Kato, S., Fox, J. C., Okamoto, K., Sakata, K., Morimatsu, M. & Shigemori, M. (2002) Int. J. Oncol. 21, 629–636.12168110 / Int. J. Oncol. (2002)

Dates

Type	When
Created	21 years, 7 months ago (Jan. 20, 2004, 12:54 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:54 a.m.)
Indexed	3 weeks ago (Aug. 7, 2025, 4:53 a.m.)
Issued	21 years, 7 months ago (Jan. 7, 2004)
Published	21 years, 7 months ago (Jan. 7, 2004)
Published Online	21 years, 7 months ago (Jan. 7, 2004)
Published Print	21 years, 7 months ago (Jan. 20, 2004)

Funders 0

None

BibTeX

@article{Kondo_2004, title={Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0307618100}, DOI={10.1073/pnas.0307618100}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kondo, Toru and Setoguchi, Takao and Taga, Tetsuya}, year={2004}, month=jan, pages={781–786} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        7
      ]
    ],
    "date-time": "2025-08-07T08:53:16Z",
    "timestamp": 1754556796414
  },
  "reference-count": 37,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "3",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        1,
        20
      ]
    ]
  },
  "abstract": "<jats:p>\n            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\n            <jats:italic>in vivo</jats:italic>\n            malignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cells\n            <jats:italic>in vitro</jats:italic>\n            and\n            <jats:italic>in vivo</jats:italic>\n            . 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.\n          </jats:p>",
  "DOI": "10.1073/pnas.0307618100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2004,
        1,
        20
      ]
    ],
    "date-time": "2004-01-20T17:54:00Z",
    "timestamp": 1074621240000
  },
  "page": "781-786",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 779,
  "title": "Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line",
  "prefix": "10.1073",
  "volume": "101",
  "author": [
    {
      "given": "Toru",
      "family": "Kondo",
      "sequence": "first",
      "affiliation": [
        {
          "name": "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"
        }
      ]
    },
    {
      "given": "Takao",
      "family": "Setoguchi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "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"
        }
      ]
    },
    {
      "given": "Tetsuya",
      "family": "Taga",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "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"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2004,
        1,
        7
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-4827(65)90211-9"
    },
    {
      "key": "e_1_3_2_2_2",
      "first-page": "137",
      "volume": "2",
      "year": "1982",
      "unstructured": "Poste, G. & Greig, R. (1982) Invasion Metastasis 2, 137\u2013176.6765249",
      "journal-title": "Invasion Metastasis"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/bjc.1983.96"
    },
    {
      "key": "e_1_3_2_4_2",
      "first-page": "6",
      "volume": "70",
      "year": "1994",
      "unstructured": "Sell, S. & Pierce, G. B. (1994) Lab. Invest 70, 6\u201322.8302019",
      "journal-title": "Lab. Invest"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35102167"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1470-2045(02)00820-3"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s004010050730"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2990.1998.00132.x"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnen/61.4.307"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.903001"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1097/00019052-200112000-00002"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80783-7"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.289.5485.1754"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.230146497"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0361-9230(01)00777-8"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200210110"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm837"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc706"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.183.4.1797"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.26.15665"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm0901-1028"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.192276999"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/333560a0"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/333562a0"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(88)90392-3"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7682010"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/neu.480250705"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.19-11-04462.1999"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/stem.200011"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/1097-0320(20000701)40:3<245::AID-CYTO10>3.0.CO;2-5"
    },
    {
      "key": "e_1_3_2_31_2",
      "first-page": "813",
      "volume": "63",
      "year": "1956",
      "unstructured": "Makino, S. (1956) Ann. N.Y. Acad. Sci. 63, 813\u2013883.",
      "journal-title": "Ann. N.Y. Acad. Sci."
    },
    {
      "key": "e_1_3_2_32_2",
      "first-page": "1544",
      "volume": "24",
      "year": "1964",
      "unstructured": "Kleinsmith, L. J. & Pierce, G. B. (1964) Cancer Res. 24, 1544\u20131552.14234000",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_2_33_2",
      "first-page": "80",
      "volume": "6",
      "year": "1992",
      "unstructured": "Gale, R. P. & Butturini, A. (1992) Leukemia 6, 80\u201385.1548943",
      "journal-title": "Leukemia"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V98.4.1166"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0530291100"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0093-7754(01)90279-9"
    },
    {
      "key": "e_1_3_2_37_2",
      "first-page": "629",
      "volume": "21",
      "year": "2002",
      "unstructured": "Aoki, T., Kato, S., Fox, J. C., Okamoto, K., Sakata, K., Morimatsu, M. & Shigemori, M. (2002) Int. J. Oncol. 21, 629\u2013636.12168110",
      "journal-title": "Int. J. Oncol."
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0307618100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T12:54:29Z",
    "timestamp": 1649768069000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0307618100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        1,
        7
      ]
    ]
  },
  "references-count": 37,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2004,
          1,
          20
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0307618100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0307618100",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1018004.206554",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2004,
        1,
        7
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-09-01",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2004-01-07",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}