Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

The Cancer Stem Cell Theory: Is It Correct?

  • Yoo, Min-Hyuk (Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health) ;
  • Hatfield, Dolph L. (Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health)
  • Received : 2008.05.15
  • Accepted : 2008.07.28
  • Published : 2008.11.30
⟨ Previous Next ⟩

Abstract

The cancer stem cell hypothesis posits that tumor growth is driven by a rare subpopulation of cells, designated cancer stem cells (CSC). Studies supporting this theory are based in large part on xenotransplantation experiments wherein human cancer cells are grown in immunocompromised mice and only CSC, often constituting less than 1% of the malignancy, generate tumors. Herein, we show that all colonies derived from randomly chosen single cells in mouse lung and breast cancer cell lines form tumors following allografting histocompatible mice. Our study suggests that the majority of malignant cells rather than CSC can sustain tumors and that the cancer stem cell theory must be reevaluated.

Keywords

Acknowledgement

Supported by : National Institutes of Health, National Cancer Institute, Center for Cancer Research

References

  1. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. (2003). Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983-3988
  2. Bertram, J.S., and Janik, P. (1980). Establishment of a cloned line of Lewis Lung Carcinoma cells adapted to cell culture. Cancer Lett. 11, 63-73 https://doi.org/10.1016/0304-3835(80)90130-5
  3. Bonnet, D., and Dick, J.E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3, 730-737 https://doi.org/10.1038/nm0797-730
  4. Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H., Jones, D.L., Visvader, J., Weissman, I.L., and Wahl, G.M. (2006). Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66, 9339-9344 https://doi.org/10.1158/0008-5472.CAN-06-3126
  5. Dick, J.E. (2003). Breast cancer stem cells revealed. Proc. Natl. Acad. Sci. USA 100, 3547-3549
  6. Grichnik, J.M. (2006). Genomic instability and tumor stem cells. J. Invest. Dermatol. 126, 1214-1216 https://doi.org/10.1038/sj.jid.5700240
  7. Hope, K.J., Jin, L., and Dick, J.E. (2004). Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat. Immunol. 5, 738-743 https://doi.org/10.1038/ni1080
  8. Huff, C.A., Matsui, W.H., Douglas Smith, G., and Jones, R.J. (2006). Strategies to eliminate cancer stem cells: clinical implications. Eur. J. Cancer. 42, 1293-1297 https://doi.org/10.1016/j.ejca.2006.01.045
  9. Jordan, C.T. (2004). Cancer stem cell biology: from leukemia to solid tumors. Curr. Opin. Cell Biol. 16, 708-712 https://doi.org/10.1016/j.ceb.2004.09.002
  10. Kelly, P.N., Dakic, A., Adams, J.M., Nutt, S.L., and Strasser, A. (2007). Tumor growth need not be driven by rare cancer stem cells. Science 317, 337 https://doi.org/10.1126/science.1142596
  11. Kennedy, J.A., Barabe, F., Poeppl, A.G., Wang, J.C., and Dick, J.E. (2007). Comment on "Tumor growth need not be driven by rare cancer stem cells". Science 318, 1722
  12. Lee, J., Kotliarova, S., Kotliarov, Y., Li, A., Su, Q., Donin, N.M., Pastorino, S., Purow, B.W., Christopher, N., Zhang, W., et al. (2006). Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9, 391-403 https://doi.org/10.1016/j.ccr.2006.03.030
  13. Massard, C., Deutsch, E., and Soria, J.C. (2006).Tumour stem celltargeted treatment: elimination or differentiation. Ann. Oncol. 17, 1620-1624 https://doi.org/10.1093/annonc/mdl074
  14. O'Brien, C.A., Pollett, A., Gallinger, S., and Dick, J.E. (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106-110 https://doi.org/10.1038/nature05372
  15. Polyak, K. (2007). Breast cancer: origins and evolution. J. Clin. Invest. 117, 3155-3163 https://doi.org/10.1172/JCI33295
  16. Rockwell, S.C., Kallman, R F., and Fajardo, L.F. (1972). Characteristics of a serially transplanted mouse mammary tumor and its tissue-culture-adapted derivative. J. Natl. Cancer Inst. 49, 735-749
  17. Singh, S.K., Clarke, I.D., Hide, T., and Dirks, P.B. (2004a). Cancer stem cells in nervous system tumors. Oncogene 23, 7267-7273 https://doi.org/10.1038/sj.onc.1207946
  18. Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004b). Identification of human brain tumour initiating cells. Nature 432, 396-401 https://doi.org/10.1038/nature03128
  19. Stingl, J., and Caldas, C. (2007). Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat. Rev. Cancer 7, 791-799 https://doi.org/10.1038/nrc2212
  20. Wang, S., Garcia, A.J., Wu, M., Lawson, D.A., Witte, O.N., and Wu, H. (2006). Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc. Natl. Acad. Sci. USA 103, 1480-1485
  21. Yang, X.F. (2007). Immunology of stem cells and cancer stem cells. Cell Mol. Immunol. 4, 161-171
  22. Yoo, M.H., Xu, X.M., Carlson, B.A., Gladyshev, V.N., and Hatfield, D.L. (2006). Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of lung carcinoma cells. J. Biol. Chem. 281, 13005-13008 https://doi.org/10.1074/jbc.C600012200