Thalhauser Craig J, Sankar Tejas, Preul Mark C, Kuang Yang
Dept. of Mathematics and Statistics, Arizona State University, Tempe, AZ 85287, USA.
Bull Math Biol. 2009 Apr;71(3):585-601. doi: 10.1007/s11538-008-9372-8. Epub 2008 Dec 9.
We investigate a new model of tumor growth in which cell motility is considered an explicitly separate process from growth. Bulk tumor expansion is modeled by individual cell motility in a density-dependent diffusion process. This model is implemented in the context of an in vivo system, the tumor cord. We investigate numerically microscale density distributions of different cell classes and macroscale whole tumor growth rates as functions of the strength of transitions between classes. Our results indicate that the total tumor growth follows a classical von Bertalanffy growth profile, as many in vivo tumors are observed to do. This provides a quick validation for the model hypotheses. The microscale and macroscale properties are both sensitive to fluctuations in the transition parameters, and grossly adopt one of two phenotypic profiles based on their parameter regime. We analyze these profiles and use the observations to classify parameter regimes by their phenotypes. This classification yields a novel hypothesis for the early evolutionary selection of the metastatic phenotype by selecting against less motile cells which grow to higher densities and may therefore induce local collapse of the vascular network.
我们研究了一种新的肿瘤生长模型,其中细胞运动被视为与生长明确分开的过程。大块肿瘤的扩张通过密度依赖性扩散过程中的单个细胞运动来建模。该模型是在体内系统——肿瘤索的背景下实现的。我们数值研究了不同细胞类别的微观尺度密度分布以及宏观尺度的整个肿瘤生长速率,它们是类别之间转变强度的函数。我们的结果表明,总的肿瘤生长遵循经典的冯·贝塔朗菲生长曲线,正如许多体内肿瘤所观察到的那样。这为模型假设提供了快速验证。微观尺度和宏观尺度特性都对转变参数的波动敏感,并根据其参数范围大致采用两种表型曲线之一。我们分析这些曲线,并利用这些观察结果按表型对参数范围进行分类。这种分类通过选择生长到更高密度且可能因此导致血管网络局部塌陷的运动性较差的细胞,为转移表型的早期进化选择提出了一个新的假设。