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Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity

Author

Listed:
  • Andriy Marusyk

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Doris P. Tabassum

    (Dana-Farber Cancer Institute
    BBS Program, Harvard Medical School)

  • Philipp M. Altrock

    (Dana-Farber Cancer Institute
    Harvard School of Public Health
    Program for Evolutionary Dynamics, Harvard University)

  • Vanessa Almendro

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Franziska Michor

    (Dana-Farber Cancer Institute
    Harvard School of Public Health)

  • Kornelia Polyak

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School
    BBS Program, Harvard Medical School)

Abstract

Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

Suggested Citation

  • Andriy Marusyk & Doris P. Tabassum & Philipp M. Altrock & Vanessa Almendro & Franziska Michor & Kornelia Polyak, 2014. "Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity," Nature, Nature, vol. 514(7520), pages 54-58, October.
    • Handle: RePEc:nat:nature:v:514:y:2014:i:7520:d:10.1038_nature13556
    DOI: 10.1038/nature13556
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    Cited by:

    1. Lavrentovich, Maxim O. & Nelson, David R., 2015. "Survival probabilities at spherical frontiers," Theoretical Population Biology, Elsevier, vol. 102(C), pages 26-39.
    2. Bernardo P de Almeida & André F Vieira & Joana Paredes & Mónica Bettencourt-Dias & Nuno L Barbosa-Morais, 2019. "Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome," PLOS Computational Biology, Public Library of Science, vol. 15(3), pages 1-31, March.
    3. Ohtsuki, Hisashi & Innan, Hideki, 2017. "Forward and backward evolutionary processes and allele frequency spectrum in a cancer cell population," Theoretical Population Biology, Elsevier, vol. 117(C), pages 43-50.

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