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Tumor Evolution in Space: The Effects of Competition Colonization Tradeoffs on Tumor Invasion Dynamics

机译:肿瘤在空间中的演变:竞争殖民权衡对肿瘤入侵动力学的影响。

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摘要

We apply competition colonization tradeoff models to tumor growth and invasion dynamics to explore the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core. Spatially, ecologically, and evolutionarily explicit partial differential equation models of tumor growth confirm that spatial invasion produces selection pressure for motile phenotypes. The effects of the invasive phenotype on normal adjacent tissue determine the patterns of growth and phenotype distribution. If tumor cells do not destroy their environment, colonizer and competitive phenotypes coexist with the former localized at the invasion front and the latter, to the tumor interior. If tumors cells do destroy their environment, then cell motility is strongly selected resulting in accelerated invasion speed with time. Our results suggest that the widely observed genetic heterogeneity within cancers may not be the stochastic effect of random mutations. Rather, it may be the consequence of predictable variations in environmental selection forces and corresponding phenotypic adaptations.
机译:我们将竞争定殖权衡模型应用于肿瘤生长和侵袭动力学,以探索以下假设:与核心细胞相比,不同的选择力将导致肿瘤浸润前沿细胞的可预测表型差异。肿瘤生长的空间,生态和进化显式偏微分方程模型证实,空间入侵会产生运动表型的选择压力。侵袭性表型对正常邻近组织的影响决定了生长和表型分布的模式。如果肿瘤细胞不破坏其环境,则定居者和竞争性表型与前者位于侵袭前沿,而后者位于肿瘤内部。如果肿瘤细胞确实破坏了周围环境,那么强烈选择细胞运动性,从而随着时间的推移加速入侵速度。我们的结果表明,癌症内广泛观察到的遗传异质性可能不是随机突变的随机效应。而是可能是环境选择力的可预测变化和相应的表型适应的结果。

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