A multiscale model for avascular tumor growth
A multiscale model for avascular tumor growth
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DOI：
10.1529/biophysj.105.060640
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Freyer, JP
中科院分区：
文献类型：
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作者：
Jiang, Y;Pjesivac-Grbovic, J;Freyer, JP
了解肿瘤复杂性的愿望已经产生了描述肿瘤微环境的数学模型。我们提出了一个新的数学模型，为无血管肿瘤的生长和发展，跨越三个不同的尺度。在细胞水平上，晶格蒙特卡罗模型描述细胞动力学（增殖、粘附和生存能力）。在亚细胞水平上，布尔网络调节控制细胞周期的蛋白质的表达。在细胞外水平，反应扩散方程描述了化学动力学（营养物、废物、生长促进剂和抑制剂浓度）。采用多细胞球体实验数据确定模拟参数。从单个肿瘤细胞开始，该模型产生了无血管肿瘤，定量模拟多细胞球体的实验测量。基于模拟，我们预测：1)肿瘤细胞存活所需的微环境条件；2)生长促进剂和抑制剂的扩散系数在10（-6）和10(-7)cm(2)/ h之间，对应于80- 90kda大小的分子。在相同的参数下，该模型也能准确预测不同外部营养供给条件下的球形生长曲线。
The desire to understand tumor complexity has given rise to mathematical models to describe the tumor microenvironment. We present a new mathematical model for avascular tumor growth and development that spans three distinct scales. At the cellular level, a lattice Monte Carlo model describes cellular dynamics (proliferation, adhesion, and viability). At the subcellular level, a Boolean network regulates the expression of proteins that control the cell cycle. At the extracellular level, reaction-diffusion equations describe the chemical dynamics (nutrient, waste, growth promoter, and inhibitor concentrations). Data from experiments with multicellular spheroids were used to determine the parameters of the simulations. Starting with a single tumor cell, this model produces an avascular tumor that quantitatively mimics experimental measurements in multicellular spheroids. Based on the simulations, we predict: 1), the microenvironmental conditions required for tumor cell survival; and 2), growth promoters and inhibitors have diffusion coefficients in the range between 10(-6) and 10(-7) cm(2)/ h, corresponding to molecules of size 80-90 kDa. Using the same parameters, the model also accurately predicts spheroid growth curves under different external nutrient supply conditions.