Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts.

Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts.
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癌细胞亚群之间的动力学揭示了一个协调分层和随机概念的模型

DOI:
10.1371/journal.pone.0084654
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wang Y
Wang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang W;Quan Y;Fu Q;Liu Y;Liang Y;Wu J;Yang G;Luo C;Ouyang Q;Wang Y

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肿瘤通常是异质性的,其中不同表型的肿瘤细胞具有不同的性质。对于科学和临床利益,了解它们的性质和不同表型之间的动态变化,特别是在放射治疗和/或化学治疗下,是至关重要的。目前有两个有争议的模型描述肿瘤异质性,癌症干细胞(CSC)模型和随机模型。为了澄清这一争议,我们通过原位免疫荧光测量了细胞不同分裂类型和转变的概率。基于实验数据,我们构建了一个模型,结合CSC的随机概念,既存在独特的CSC亚群和随机过渡从NSCCs到CSC。结果表明,该模型能够较好地模拟肿瘤干细胞与非干细胞之间的动态变化。进一步的研究也表明,该模型可以用来描述辐射处理后两个亚群的动态。更重要的是,分析表明,只有当从NSCC到CSC的随机转变发生时,才能实现实验可检测的平衡CSC比例,这表明肿瘤异质性可能存在于CSC和随机概念协调的模型中。基于实验参数的数学模型有助于更好地理解肿瘤异质性,并为研究放射治疗过程中CSC亚群的动态变化提供参考。
Tumors are often heterogeneous in which tumor cells of different phenotypes have distinct properties. For scientific and clinical interests, it is of fundamental importance to understand their properties and the dynamic variations among different phenotypes, specifically under radio- and/or chemo-therapy. Currently there are two controversial models describing tumor heterogeneity, the cancer stem cell (CSC) model and the stochastic model. To clarify the controversy, we measured probabilities of different division types and transitions of cells via in situ immunofluorescence. Based on the experiment data, we constructed a model that combines the CSC with the stochastic concepts, showing the existence of both distinctive CSC subpopulations and the stochastic transitions from NSCCs to CSCs. The results showed that the dynamic variations between CSCs and non-stem cancer cells (NSCCs) can be simulated with the model. Further studies also showed that the model can be used to describe the dynamics of the two subpopulations after radiation treatment. More importantly, analysis demonstrated that the experimental detectable equilibrium CSC proportion can be achieved only when the stochastic transitions from NSCCs to CSCs occur, indicating that tumor heterogeneity may exist in a model coordinating with both the CSC and the stochastic concepts. The mathematic model based on experimental parameters may contribute to a better understanding of the tumor heterogeneity, and provide references on the dynamics of CSC subpopulation during radiotherapy.
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