The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity
The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity
复制标题
表征可逆表型可塑性癌症动力学的超调和表型平衡
DOI：
10.1016/j.jtbi.2015.11.008
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发表时间：
2016-02-07
影响因子：
2
通讯作者：
Zhou, Da
中科院分区：
文献类型：
--
作者：
Chen, Xiufang;Wang, Yue;Zhou, Da
表型可塑性范式揭示了不同癌细胞表型之间的可逆关系，扩展了经典癌症干细胞（CSC）理论提出的细胞层次。由于表型可塑性究竟是对层次模型的重要改进还是仅仅是对层次模型的微小扩展，目前尚不清楚，因此有必要探讨表征可逆表型可塑性的动态行为。在这项研究中，我们比较了层次模型和可逆模型在预测生物学实验中观察到的细胞状态动力学。我们的研究结果表明，在描述癌细胞群的长期稳定性（表型平衡）和短期瞬态动力学（超调）方面，层次模型比可逆模型有明显的缺点。在一个非常特殊的情况下，由于每种细胞类型的总体增长是相同的，层次模型既不能预测表型平衡也不能预测超调，而可逆模型成功地预测了两者。尽管层次模型的性能可以通过放松特定的假设而得到改善，但其对表型平衡的预测强烈依赖于一个在生物学实验中可能不现实的先决条件。此外，在捕获CSCs和非CSCs的过调量方面，它仍然没有表现出像可逆模型那样丰富的动态。相比之下，可逆模型更有可能正确预测表型混合的稳定性和各种类型的超调行为。(C) 2015 Elsevier Ltd.版权所有。
The paradigm of phenotypic plasticity indicates reversible relations of different cancer cell phenotypes, which extends the cellular hierarchy proposed by the classical cancer stem cell (CSC) theory. Since it is still questionable if the phenotypic plasticity is a crucial improvement to the hierarchical model or just a minor extension to it it is worthwhile to explore the dynamic behavior characterizing the reversible phenotypic plasticity. In this study we compare the hierarchical model and the reversible model in predicting the cell-state dynamics observed in biological experiments. Our results show that the hierarchical model shows significant disadvantages over the reversible model in describing both long-term stability (phenotypic equilibrium) and short-term transient dynamics (overshoot) in cancer cell populations. In a very specific case in which the total growth of population due to each cell type is identical, the hierarchical model predicts neither phenotypic equilibrium nor overshoot, whereas the reversible model succeeds in predicting both of them. Even though the performance of the hierarchical model can be improved by relaxing the specific assumption, its prediction to the phenotypic equilibrium strongly depends on a precondition that may be unrealistic in biological experiments. Moreover, it still does not show as rich dynamics as the reversible model in capturing the overshoots of both CSCs and non-CSCs. By comparison, it is more likely for the reversible model to correctly predict the stability of the phenotypic mixture and various types of overshoot behavior. (C) 2015 Elsevier Ltd. All rights reserved.