Salimi Sartakhti Javad, Manshaei Mohammad Hossein, Sadeghi Mehdi
Department of Electrical and Computer Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
School of Biological Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
J Theor Biol. 2017 Jan 7;412:17-26. doi: 10.1016/j.jtbi.2016.09.019. Epub 2016 Sep 23.
One of the main steps in solid cancers to invade surrounding tissues is degradation of tissue barriers in the extracellular matrix. This operation that leads to initiate, angiogenesis and metastasis to other organs, is essentially consequence of collapsing dynamic balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). In this work, we model the MMP-TIMP interaction in both normal tissue and invasive cancer using evolutionary game theory. Our model explains how invasive cancer cells get the upper hand in MMP-TIMP imbalance scenarios. We investigate dynamics of them over time and discuss stable and nonstable states in the population. Numerical simulations presented here provide the identification of key genotypic features in the tumor invasion and a natural description for phenotypic variability. The simulation results are consistent with the experimental results in vitro observations presented in medical literature. Finally, by the provided results the necessary conditions to inhibit cancer invasion or prolong its course are explained. In this way, two therapeutic approaches with respect to how they could meet the required conditions are considered.
实体癌侵袭周围组织的主要步骤之一是细胞外基质中组织屏障的降解。这种导致启动、血管生成以及转移至其他器官的作用，本质上是基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）之间动态平衡崩溃的结果。在这项工作中，我们使用进化博弈论对正常组织和侵袭性癌症中的MMP - TIMP相互作用进行建模。我们的模型解释了侵袭性癌细胞如何在MMP - TIMP失衡的情况下占据上风。我们研究了它们随时间的动态变化，并讨论了种群中的稳定和非稳定状态。此处给出的数值模拟提供了肿瘤侵袭中关键基因型特征的识别以及表型变异性的自然描述。模拟结果与医学文献中给出的体外实验结果一致。最后，通过所提供的结果解释了抑制癌症侵袭或延长其进程的必要条件。通过这种方式，考虑了两种关于如何满足所需条件的治疗方法。
