An evolutionary explanation for the presence of cancer nonstem cells in neoplasms

Authors

  • Kathleen Sprouffske,

    Corresponding authorCurrent affiliation:
    1. Institute for Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland
    • Genomics and Computational Biology Program, Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
    Search for more papers by this author
  • C. Athena Aktipis,

    1. Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, Department of Surgery, University of California San Francisco, San Francisco, CA, USA
    2. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, USA
    3. Department of Psychology, Arizona State University, Tempe, AZ, USA
    Search for more papers by this author
  • Jerald P. Radich,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    Search for more papers by this author
  • Martin Carroll,

    1. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
    Search for more papers by this author
  • Aurora M. Nedelcu,

    1. Department of Biology, University of New Brunswick, Fredericton, NB, Canada
    Search for more papers by this author
  • Carlo C. Maley

    1. Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, Department of Surgery, University of California San Francisco, San Francisco, CA, USA
    Search for more papers by this author

Correspondence

Kathleen Sprouffske, Institute for Evolutionary Biology and Environmental Studies, University of Zurich, 8003 Zurich, Switzerland.

Tel.: +41 44 635 6151;

Fax: +41 44 635 6144;

e-mail: kathleen.sprouffske@ieu.uzh.ch

Abstract

Contrary to conventional views that assume all cells in a neoplasm can propagate the tumor, the cancer stem cell hypothesis posits that only a fraction of the cells (the cancer stem cells) can act as tumor-propagating cells, while most of the tumor is composed of cells with limited replication potential. Here, we offer an evolutionary approach to this controversy. We used several evolutionary, computational models to investigate cancer cell dynamics and conditions consistent with the stem cell hypothesis. Our models predict that if selection acts at the cell level, neoplasms should be primarily comprised of cancer stem cells, in contrast to experimental data indicating that neoplasms contain large fractions of cancer nonstem cells. We explore several solutions explaining the paradoxical existence of cancer nonstem cells in neoplasms, including the possibility that selection acts at the level of multicellular proliferative units.

Ancillary