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Including Blood Vasculature into a Game-Theoretic Model of Cancer Dynamics

Author

Listed:
  • Li You

    (Department of Molecular Genetics, Erasmus Medical Center, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands
    Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands
    Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA)

  • Maximilian von Knobloch

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Teresa Lopez

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Vanessa Peschen

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Sidney Radcliffe

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Praveen Koshy Sam

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Frank Thuijsman

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands)

  • Kateřina Staňková

    (Department of Data Science and Knowledge Engineering, Maastricht University, Bouillonstraat 8-10, 6211 LH Maastricht, The Netherlands
    Delft Institute of Applied Mathematics, Delft University of Technology, Mourik Broekmanweg 6, 2628 XE Delft, The Netherlands)

  • Joel S. Brown

    (Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA)

Abstract

For cancer, we develop a 2-D agent-based continuous-space game-theoretical model that considers cancer cells’ proximity to a blood vessel. Based on castrate resistant metastatic prostate cancer (mCRPC), the model considers the density and frequency (eco-evolutionary) dynamics of three cancer cell types: those that require exogenous testosterone ( T + ), those producing testosterone ( T P ), and those independent of testosterone ( T − ). We model proximity to a blood vessel by imagining four zones around the vessel. Zone 0 is the blood vessel. As rings, zones 1–3 are successively farther from the blood vessel and have successively lower carrying capacities. Zone 4 represents the space too far from the blood vessel and too poor in nutrients for cancer cell proliferation. Within the other three zones that are closer to the blood vessel, the cells’ proliferation probabilities are determined by zone-specific payoff matrices. We analyzed how zone width, dispersal, interactions across zone boundaries, and blood vessel dynamics influence the eco-evolutionary dynamics of cell types within zones and across the entire cancer cell population. At equilibrium, zone 3’s composition deviates from its evolutionary stable strategy (ESS) towards that of zone 2. Zone 2 sees deviations from its ESS because of dispersal from zones 1 and 3; however, its composition begins to resemble zone 1’s more so than zone 3’s. Frequency-dependent interactions between cells across zone boundaries have little effect on zone 2’s and zone 3’s composition but have decisive effects on zone 1. The composition of zone 1 diverges dramatically from both its own ESS, but also that of zone 2. That is because T + cells (highest frequency in zone 1) benefit from interacting with T P cells (highest frequency in zone 2). Zone 1 T + cells interacting with cells in zone 2 experience a higher likelihood of encountering a T P cell than when restricted to their own zone. As expected, increasing the width of zones decreases these impacts of cross-boundary dispersal and interactions. Increasing zone widths increases the persistence likelihood of the cancer subpopulation in the face of blood vessel dynamics, where the vessel may die or become occluded resulting in the “birth” of another blood vessel elsewhere in the space. With small zone widths, the cancer cell subpopulations cannot persist. With large zone widths, blood vessel dynamics create cancer cell subpopulations that resemble the ESS of zone 3 as the larger area of zone 3 and its contribution to cells within the necrotic zone 4 mean that zones 3 and 4 provide the likeliest colonizers for the new blood vessel. In conclusion, our model provides an alternative modeling approach for considering density-dependent, frequency-dependent, and dispersal dynamics into cancer models with spatial gradients around blood vessels. Additionally, our model can consider the occurrence of circulating tumor cells (cells that disperse into the blood vessel from zone 1) and the presence of live cancer cells within the necrotic regions of a tumor.

Suggested Citation

  • Li You & Maximilian von Knobloch & Teresa Lopez & Vanessa Peschen & Sidney Radcliffe & Praveen Koshy Sam & Frank Thuijsman & Kateřina Staňková & Joel S. Brown, 2019. "Including Blood Vasculature into a Game-Theoretic Model of Cancer Dynamics," Games, MDPI, vol. 10(1), pages 1-22, March.
  • Handle: RePEc:gam:jgames:v:10:y:2019:i:1:p:13-:d:212809
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    References listed on IDEAS

    as
    1. Jingsong Zhang & Jessica J. Cunningham & Joel S. Brown & Robert A. Gatenby, 2017. "Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    2. R. A. Gatenby & J. J. Cunningham & J. S. Brown, 2014. "Evolutionary triage governs fitness in driver and passenger mutations and suggests targeting never mutations," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    3. D. Basanta & H. Hatzikirou & A. Deutsch, 2008. "Studying the emergence of invasiveness in tumours using game theory," The European Physical Journal B: Condensed Matter and Complex Systems, Springer;EDP Sciences, vol. 63(3), pages 393-397, June.
    4. Elena Hurlbut & Ethan Ortega & Igor V. Erovenko & Jonathan T. Rowell, 2018. "Game Theoretical Model of Cancer Dynamics with Four Cell Phenotypes," Games, MDPI, vol. 9(3), pages 1-16, September.
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    Cited by:

    1. Benjamin Wölfl & Hedy te Rietmole & Monica Salvioli & Artem Kaznatcheev & Frank Thuijsman & Joel S. Brown & Boudewijn Burgering & Kateřina Staňková, 2022. "The Contribution of Evolutionary Game Theory to Understanding and Treating Cancer," Dynamic Games and Applications, Springer, vol. 12(2), pages 313-342, June.

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