Cellular potts modeling of tumor growth, tumor invasion, and tumor evolution.
Cellular potts modeling of tumor growth, tumor invasion, and tumor evolution.
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DOI：
10.3389/fonc.2013.00087
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发表时间：
2013
影响因子：
4.7
通讯作者：
Merks RM
中科院分区：
文献类型：
--
作者：
Szabó A;Merks RM
尽管可用的分子数据越来越丰富，但肿瘤的生长、肿瘤侵入健康组织以及肿瘤对治疗的反应仍然知之甚少。虽然基因突变通常是癌症发展的第一步，但突变细胞要想在组织中存活，就必须与其他健康或患病细胞竞争，例如变得更有活力、更有粘性或繁殖更快。因此，细胞表型决定了癌细胞在与其邻居的竞争中是否成功，而不考虑导致表型改变的基因突变或生理改变。什么样的表型可以使细胞在健康细胞和癌细胞的环境中“成功”，以及如何成功？为了更深入地了解这个问题，一个广泛使用的工具是基于细胞的建模。基于细胞的模型构成了一类模拟细胞间生物物理和分子相互作用的计算的、基于主体的模型。最广泛使用的基于细胞的建模形式之一是细胞Potts模型（CPM），这是一种基于网格的多粒子基于细胞的建模方法。CPM已经成为一种流行的和可访问的多细胞过程建模机制的方法，包括细胞分选，原肠胚形成或血管生成。CPM解释了生物物理细胞特性，包括细胞增殖、细胞运动和细胞粘附，这些在癌症中起关键作用。多尺度模型是通过扩展细胞内代谢、生长和信号传导等过程来构建的。在这里，我们回顾了CPM在模拟肿瘤生长、肿瘤侵袭和肿瘤进展方面的应用。我们认为，CPM的可访问性和灵活性，以及它对细胞和组织生物物理学的准确、粗粒度和计算效率的表示，使CPM成为肿瘤发展中细胞过程建模的首选方法。
Despite a growing wealth of available molecular data, the growth of tumors, invasion of tumors into healthy tissue, and response of tumors to therapies are still poorly understood. Although genetic mutations are in general the first step in the development of a cancer, for the mutated cell to persist in a tissue, it must compete against the other, healthy or diseased cells, for example by becoming more motile, adhesive, or multiplying faster. Thus, the cellular phenotype determines the success of a cancer cell in competition with its neighbors, irrespective of the genetic mutations or physiological alterations that gave rise to the altered phenotype. What phenotypes can make a cell “successful” in an environment of healthy and cancerous cells, and how? A widely used tool for getting more insight into that question is cell-based modeling. Cell-based models constitute a class of computational, agent-based models that mimic biophysical and molecular interactions between cells. One of the most widely used cell-based modeling formalisms is the cellular Potts model (CPM), a lattice-based, multi particle cell-based modeling approach. The CPM has become a popular and accessible method for modeling mechanisms of multicellular processes including cell sorting, gastrulation, or angiogenesis. The CPM accounts for biophysical cellular properties, including cell proliferation, cell motility, and cell adhesion, which play a key role in cancer. Multiscale models are constructed by extending the agents with intracellular processes including metabolism, growth, and signaling. Here we review the use of the CPM for modeling tumor growth, tumor invasion, and tumor progression. We argue that the accessibility and flexibility of the CPM, and its accurate, yet coarse-grained and computationally efficient representation of cell and tissue biophysics, make the CPM the method of choice for modeling cellular processes in tumor development.