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Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma

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  • Javad Salimi Sartakhti
  • Mohammad Hossein Manshaei
  • Soroosh Bateni
  • Marco Archetti

Abstract

Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts) exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

Suggested Citation

  • Javad Salimi Sartakhti & Mohammad Hossein Manshaei & Soroosh Bateni & Marco Archetti, 2016. "Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-17, December.
    • Handle: RePEc:plo:pone00:0168856
    DOI: 10.1371/journal.pone.0168856
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    References listed on IDEAS

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    1. Allison S. Cleary & Travis L. Leonard & Shelley A. Gestl & Edward J. Gunther, 2014. "Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers," Nature, Nature, vol. 508(7494), pages 113-117, April.
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    Cited by:

    1. Marco Archetti, 2018. "How to Analyze Models of Nonlinear Public Goods," Games, MDPI, vol. 9(2), pages 1-15, April.
    2. Ryan T. Bishop & Anna K. Miller & Matthew Froid & Niveditha Nerlakanti & Tao Li & Jeremy S. Frieling & Mostafa M. Nasr & Karl J. Nyman & Praneeth R. Sudalagunta & Rafael R. Canevarolo & Ariosto Siquei, 2024. "The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Javad Salimi Sartakhti & Mohammad Hossein Manshaei & Marco Archetti, 2018. "Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits," Games, MDPI, vol. 9(2), pages 1-11, May.
    4. Javad Salimi Sartakhti & Mohammad Hossein Manshaei & David Basanta & Mehdi Sadeghi, 2017. "Evolutionary emergence of angiogenesis in avascular tumors using a spatial public goods game," PLOS ONE, Public Library of Science, vol. 12(4), pages 1-17, April.

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