Game theory of tumor–stroma interactions in multiple myeloma

Effect of nonlinear benefits

Javad Salimi Sartakhti, Mohammad Hossein Manshaei, Marco Archetti

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions.

Original languageEnglish (US)
Article number32
JournalGames
Volume9
Issue number2
DOIs
StatePublished - Jun 1 2018

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Game theory
Game Theory
Growth Factors
Cell
Interaction
Nonlinear Effects
Osteoblasts
Evolutionary Game Theory
Cell growth
Beam plasma interactions
Evolutionary Dynamics
Linear Function
Therapy
Cells
Pairwise
Linear Model
Cancer
Plasmas
Plasma
Model

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Statistics, Probability and Uncertainty
  • Applied Mathematics

Cite this

Sartakhti, Javad Salimi ; Manshaei, Mohammad Hossein ; Archetti, Marco. / Game theory of tumor–stroma interactions in multiple myeloma : Effect of nonlinear benefits. In: Games. 2018 ; Vol. 9, No. 2.
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Game theory of tumor–stroma interactions in multiple myeloma : Effect of nonlinear benefits. / Sartakhti, Javad Salimi; Manshaei, Mohammad Hossein; Archetti, Marco.

In: Games, Vol. 9, No. 2, 32, 01.06.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Game theory of tumor–stroma interactions in multiple myeloma

T2 - Effect of nonlinear benefits

AU - Sartakhti, Javad Salimi

AU - Manshaei, Mohammad Hossein

AU - Archetti, Marco

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AB - Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions.

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