Integrated Mathematical Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Exp Biol Med (Maywood). 2010 Apr;235(4):411-23. doi: 10.1258/ebm.2009.009230.
In its simplest description, a tumor is comprised of an expanding population of transformed cells supported by a surrounding microenvironment termed the tumor stroma. The tumor microenvironment has a very complex composition, including multiple types of stromal cells, a dense network of various extracellular matrix (ECM) fibers interpenetrated by the interstitial fluid and gradients of several chemical species that either are dissolved in the fluid or are bound to the ECM structure. In order to study experimentally such complex interactions between multiple players, cancer is dissected and considered at different scales of complexity, such as protein interactions, biochemical pathways, cellular functions or whole organism studies. However, the integration of information acquired from these studies into a common description is as difficult as the disease itself. Computational models of cancer can provide cancer researchers with invaluable tools that are capable of integrating the complexity into organizing principles as well as suggesting testable hypotheses. We will focus in this Minireview on mathematical models in which the whole cell is a main modeling unit. We will present a current stage of such cell-focused mathematical modeling incorporating different stromal components and their interactions with growing tumors, and discuss what modeling approaches can be undertaken to complement the in vivo and in vitro experimentation.
在最简单的描述中，肿瘤由被称为肿瘤基质的周围微环境支持的不断扩张的转化细胞群体组成。肿瘤微环境的组成非常复杂，包括多种基质细胞，各种细胞外基质 (ECM) 纤维的密集网络，这些纤维相互交织并渗透间质液，还有多种化学物质的浓度梯度，这些物质要么溶解在液体中，要么与 ECM 结构结合。为了在实验中研究这些多种参与者之间的复杂相互作用，癌症被分解并在不同的复杂程度上进行考虑，例如蛋白质相互作用、生化途径、细胞功能或整个生物体研究。然而，将从这些研究中获得的信息整合到一个共同的描述中就像疾病本身一样困难。癌症的计算模型可以为癌症研究人员提供非常有价值的工具，这些工具能够将复杂性纳入组织原则，并提出可测试的假设。在这篇综述中，我们将重点关注以整个细胞为主要建模单元的数学模型。我们将介绍当前阶段的这种以细胞为中心的数学建模，其中纳入了不同的基质成分及其与生长肿瘤的相互作用，并讨论可以采用哪些建模方法来补充体内和体外实验。
