Department of Mathematics & Statistics, University of Michigan, Dearborn, MI 48128-2406, USA.
Prog Biophys Mol Biol. 2011 Aug;106(2):353-79. doi: 10.1016/j.pbiomolbio.2011.06.006. Epub 2011 Jun 28.
Mathematical modeling and computational analysis are essential for understanding the dynamics of the complex gene networks that control normal development and homeostasis, and can help to understand how circumvention of that control leads to abnormal outcomes such as cancer. Our objectives here are to discuss the different mechanisms by which the local biochemical and mechanical microenvironment, which is comprised of various signaling molecules, cell types and the extracellular matrix (ECM), affects the progression of potentially-cancerous cells, and to present new results on two aspects of these effects. We first deal with the major processes involved in the progression from a normal cell to a cancerous cell at a level accessible to a general scientific readership, and we then outline a number of mathematical and computational issues that arise in cancer modeling. In Section 2 we present results from a model that deals with the effects of the mechanical properties of the environment on tumor growth, and in Section 3 we report results from a model of the signaling pathways and the tumor microenvironment (TME), and how their interactions affect the development of breast cancer. The results emphasize anew the complexities of the interactions within the TME and their effect on tumor growth, and show that tumor progression is not solely determined by the presence of a clone of mutated immortal cells, but rather that it can be 'community-controlled'.
数学建模和计算分析对于理解控制正常发育和内稳态的复杂基因网络的动态至关重要，并且有助于理解这种控制的规避如何导致异常结果，如癌症。我们的目标是讨论局部生化和机械微环境（由各种信号分子、细胞类型和细胞外基质 (ECM) 组成）影响潜在癌变细胞进展的不同机制，并介绍这些影响的两个方面的新结果。我们首先在一般科学读者可理解的水平上处理从正常细胞到癌细胞进展的主要过程，然后概述癌症建模中出现的一些数学和计算问题。在第 2 节中，我们呈现了一个处理环境力学特性对肿瘤生长影响的模型的结果，在第 3 节中，我们报告了一个信号通路和肿瘤微环境 (TME) 模型的结果，以及它们的相互作用如何影响乳腺癌的发展。结果再次强调了 TME 内部相互作用的复杂性及其对肿瘤生长的影响，并表明肿瘤进展不仅仅取决于突变的永生细胞克隆的存在，而是可以“社区控制”。
