Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL-33612, USA.
Math Biosci. 2011 Jan;229(1):22-9. doi: 10.1016/j.mbs.2010.10.005. Epub 2010 Oct 31.
The tumour microenvironment is known to play an important role in determining the sequence of acquired phenotypic traits that characterise cancer evolution. A more precise understanding of this role could have a major influence in the understanding of cancer growth and development, and potentially in the optimisation of innovative anti-cancer treatments delivery. However, to lead such an analysis in the basis of traditional biological experiments and observations is almost utopian given the complexity of the underlying biological processes and the typical time scales involved. In this context, computer models constitute a complementary exploratory tool. In this paper we introduce a two-dimensional cellular automaton that models key cancer cell capabilities. The model has been especially designed to mimic the behaviour of a cancer colony growing in vitro and to analyse the effect of different environmental conditions on the sequence of acquisition of phenotypic traits. Our results indicate that microenvironmental factors such as the local concentration of oxygen or nutrients and cell overcrowding may determine the expansion of the tumour colony. The results also show that tumour cells evolve and that their phenotypes adapt to the microenvironment so that environmental stress determines the dominance of particular phenotypical traits.
肿瘤微环境在决定癌症进化特征的获得性表型特征的顺序方面起着重要作用。更精确地了解这一作用可能会对癌症生长和发展有重大影响，并有可能优化创新抗癌治疗的应用。然而，考虑到潜在生物学过程的复杂性和典型的时间尺度，基于传统生物学实验和观察来进行这样的分析几乎是不可能的。在这种情况下，计算机模型构成了一种补充性的探索工具。在本文中，我们引入了一个二维细胞自动机模型，该模型模拟了关键的癌细胞功能。该模型专门设计用于模拟在体外生长的癌细胞菌落的行为，并分析不同环境条件对表型特征获得顺序的影响。我们的结果表明，微环境因素，如局部氧气或营养物质浓度和细胞过度拥挤，可能决定肿瘤菌落的扩张。结果还表明，肿瘤细胞会进化，它们的表型会适应微环境，因此环境压力决定了特定表型特征的优势。
