Cancers are the result of eco-evolutionary processes fueled by heritable phenotypic diversification and driven by environmentally dependent selection. As space represents a key growth-limiting ecological resource, the ability to gain and explore this resource is likely to be under strong selection. Using agent-based computational modeling, we explored the consequences of the interplay between phenotypic strategies centered on gaining access to new space through cell-extrinsic degradation of extracellular matrix barriers and the exploitation of this resource through maximizing cell proliferation. While cell proliferation is a cell-intrinsic property, newly accessed space represents a public good, which can benefit both producers and non-producers. We found that that this interplay results in ecological succession, enabling emergence of large, heterogenous, and highly proliferative populations. Even though in our simulations both remodeling and proliferation strategies were under strong positive selection, their interplay led to sub-clonal architecture that could be interpreted as evidence for neutral evolution, warranting cautious interpretation of inferences from sequencing of cancer genomes.

中文翻译：

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选择驱动的涉及非细胞生长促进的肿瘤进化导致克隆扩增的模式与中性解释一致

癌症是可遗传表型多样化推动的生态进化过程的结果，而环境依赖的选择驱动了癌症的发展。由于空间代表着一种关键的限制生长的生态资源，因此获取和开发这种资源的能力很可能处于强烈选择之下。使用基于代理的计算模型，我们探索了表型策略之间相互作用的结果，这些策略的中心是通过细胞外基质屏障的细胞外源性降解获得新空间，并通过最大化细胞增殖来利用这种资源。虽然细胞增殖是一种细胞固有的特性，但新进入的空间代表了一种公共物品，既可以使生产者受益，也可以使非生产者受益。我们发现，这种相互作用会导致生态演替，从而导致大型，异质且高度增殖的种群。即使在我们的模拟中，重塑和增殖策略均处于强阳性选择之下，但它们的相互作用导致亚克隆体系结构可被解释为中性进化的证据，从而保证了对癌症基因组测序推论的谨慎解释。