A multi-phenotypic cancer model with cell plasticity

DOI10.1016/J.JTBI.2014.04.039zbMATH Open1412.92166arXiv1311.6222OpenAlexW2037441536WikidataQ45534735 ScholiaQ45534735MaRDI QIDQ2415595FDOQ2415595

Authors: Da Zhou, Yue Wang, Bin Wu 

Publication date: 23 May 2019

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

Abstract: The conventional cancer stem cell (CSC) theory indicates a hierarchy of CSCs and non-stem cancer cells (NSCCs), that is, CSCs can differentiate into NSCCs but not vice versa. However, an alternative paradigm of CSC theory with reversible cell plasticity among cancer cells has received much attention very recently. Here we present a generalized multi-phenotypic cancer model by integrating cell plasticity with the conventional hierarchical structure of cancer cells. We prove that under very weak assumption, the nonlinear dynamics of multi-phenotypic proportions in our model has only one stable steady state and no stable limit cycle. This result theoretically explains the phenotypic equilibrium phenomena reported in various cancer cell lines. Furthermore, according to the transient analysis of our model, it is found that cancer cell plasticity plays an essential role in maintaining the phenotypic diversity in cancer especially during the transient dynamics. Two biological examples with experimental data show that the phenotypic conversions from NCSSs to CSCs greatly contribute to the transient growth of CSCs proportion shortly after the drastic reduction of it. In particular, an interesting overshooting phenomenon of CSCs proportion arises in three-phenotypic example. Our work may pave the way for modeling and analyzing the multi-phenotypic cell population dynamics with cell plasticity.

Full work available at URL: https://arxiv.org/abs/1311.6222

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zbMATH Keywords

transient dynamicscancer stem cell theorycell-state conversionsmulti-phenotype model

Mathematics Subject Classification ID

Medical applications (general) (92C50) Cell biology (92C37)

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Cited In (17)

• On tumoural growth and treatment under cellular dedifferentiation
• The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity
• Inference on autoregulation in gene expression with variance-to-mean ratio
• Mathematical modelling of plasticity and phenotype switching in cancer cell populations
• The phenotypic equilibrium of cancer cells: from average-level stability to path-wise convergence
• Inference on the structure of gene regulatory networks
• Replicator dynamics of cancer stem cell: selection in the presence of differentiation and plasticity
• Cell population growth kinetics in the presence of stochastic heterogeneity of cell phenotype
• Effects of a differentiating therapy on cancer-stem-cell-driven tumors
• A Bayesian statistical analysis of stochastic phenotypic plasticity model of cancer cells
• Multispecies model of cell lineages and feedback control in solid tumors
• The noise and the KISS in the cancer stem cells niche
• Transition therapy: tackling the ecology of tumor phenotypic plasticity
• A mathematical study of the impact of cell plasticity on tumour control probability
• The effects of phenotypic plasticity on the fixation probability of mutant cancer stem cells
• Negligible long-term impact of nonlinear growth dynamics on heterogeneity in models of cancer cell populations
• Modeling tumorspheres reveals cancer stem cell niche building and plasticity

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