A multi-phenotypic cancer model with cell plasticity
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Publication:2415595
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.
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Cited in
(19)- 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
- A mathematical study of the impact of cell plasticity on tumour control probability
- Transition therapy: tackling the ecology of tumor phenotypic plasticity
- On tumoural growth and treatment under cellular dedifferentiation
- Inference on the structure of gene regulatory networks
- Modeling tumorspheres reveals cancer stem cell niche building and plasticity
- The effects of phenotypic plasticity on the fixation probability of mutant cancer stem cells
- The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity
- Inference on autoregulation in gene expression with variance-to-mean ratio
- Effects of a differentiating therapy on cancer-stem-cell-driven tumors
- Cell population growth kinetics in the presence of stochastic heterogeneity of cell phenotype
- Negligible long-term impact of nonlinear growth dynamics on heterogeneity in models of cancer cell populations
- Modeling the impact of dedifferentiation on colorectal cancer growth and chemo-immunotherapy response
- Inferring absolute cell numbers from relative proportion in stochastic models with cell plasticity
- 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
- Replicator dynamics of cancer stem cell: selection in the presence of differentiation and plasticity
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