Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics

Heiko Enderling, Alexander R. A. Anderson, Mark A. J. Chaplain, Afshin Beheshti, Lynn Hlatky, Philip Hahnfeldt

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    121 Citations (Scopus)

    Abstract

    Even after a tumor is established, it can early on enter a state of dormancy marked by balanced cell proliferation and cell death. Disturbances to this equilibrium may affect cancer risk, as they may cause the eventual lifetime clinical presentation of a tumor that might otherwise have remained asymptomatic. Previously, we showed that cell death, proliferation, and migration can play a role in shifting this dynamic, making the understanding of their combined influence on tumor development essential. We developed an individual cell-based computer model of the interaction of cancer stem cells and their nonstem progeny to study early tumor dynamics. Simulations of tumor growth show that three basic components of tumor growth-cell proliferation, migration, and death-combine in unexpected ways to control tumor progression and, thus, clinical cancer risk. We show that increased proliferation capacity in nonstem tumor cells and limited cell migration overall lead to space constraints that inhibit proliferation and tumor growth. By contrast, increasing the rate of cell death produces the expected tumor size reduction in the short term, but results ultimately in paradoxical accelerated long-term growth owing to the liberation of cancer stem cells and formation of self-metastases. [Cancer Res 2009;69(22):8814-21]

    Original languageEnglish
    Pages (from-to)8814-8821
    Number of pages8
    JournalCancer Research
    Volume69
    Issue number22
    DOIs
    Publication statusPublished - 15 Nov 2009

    Keywords

    • Cancer stem cells
    • Chronic myeloid leukaemia
    • Human pancreatic cancer
    • Prostate cancer
    • Spontaneous apoptosis
    • Automaton modeling
    • Colon cancer
    • Growth
    • Therapy
    • Dynamics

    Cite this

    Enderling, H., Anderson, A. R. A., Chaplain, M. A. J., Beheshti, A., Hlatky, L., & Hahnfeldt, P. (2009). Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics. Cancer Research, 69(22), 8814-8821. https://doi.org/10.1158/0008-5472.CAN-09-2115