演化博弈论阐明糖酵解在胶质瘤进展和侵袭中的作用
Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion
摘要：
肿瘤进展已被描述为如果赘生物成为侵袭性和恶性癌症，则细胞必须获得的一系列性状或表型。虽然导致这些表型的基因突变是随机的，但其中一些突变成功和扩散的过程受到肿瘤微环境和其他表型的影响。因此，在肿瘤进展中必不可少的一些表型可能仅在先前存在其他不同表型的情况下才出现在肿瘤群体中。在本文中，我们使用演化博弈论来分析三种不同的肿瘤细胞表型之间的相互作用定义的自主生长，无氧糖酵解，和癌细胞的侵袭。该模型允许了解胶质瘤进展的某些特定方面，例如在低级别肿瘤中出现弥漫性肿瘤细胞侵袭。我们发现，侵袭性表型更可能在糖酵解表型出现后演变，这将解释恶性肿瘤中普遍存在的侵袭性生长。结果表明，增加转换为无氧糖酵解的适应性成本的疗法可能会降低出现更具侵袭性表型的可能性。
英文摘要：
Tumour progression has been described as a sequence of traits or phenotypes that cells have to acquire if the neoplasm is to become an invasive and malignant cancer. Although the genetic mutations that lead to these phenotypes are random, the process by which some of these mutations become successful and spread is influenced by the tumour microenvironment and the presence of other phenotypes. It is thus likely that some phenotypes that are essential in tumour progression will emerge in the tumour population only with the prior presence of other different phenotypes. In this paper we use evolutionary game theory to analyse the interactions between three different tumour cell phenotypes defined by autonomous growth, anaerobic glycolysis, and cancer cell invasion. The model allows to understand certain specific aspects of glioma progression such as the emergence of diffuse tumour cell invasion in low-grade tumours. We find that the invasive phenotype is more likely to evolve after the appearance of the glycolytic phenotype which would explain the ubiquitous presence of invasive growth in malignant tumours. The result suggests that therapies which increase the fitness cost of switching to anaerobic glycolysis might decrease the probability of the emergence of more invasive phenotypes
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