Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion
Evolutionary game theory elucidates the role of glycolysis in glioma progression and invasion
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DOI：
10.1111/j.1365-2184.2008.00563.x
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发表时间：
2008-12-01
影响因子：
8.5
通讯作者：
Deutsch, A.
中科院分区：
文献类型：
--
作者：
Basanta, D.;Simon, M.;Deutsch, A.
目的：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细胞扩散的过程受到肿瘤微环境和其他细胞表型的影响。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。材料与方法：在这项研究中，我们使用进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，定义为自主生长，无氧糖酵解和癌细胞侵袭。该模型使我们能够了解胶质瘤进展的某些特定方面，例如低级别肿瘤中弥漫性肿瘤细胞侵袭的出现。结果如下：我们已经发现，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侵袭性生长的普遍存在。结论：结果表明，增加转换为无氧糖酵解的健身成本的疗法可能会降低出现更具侵袭性表型的概率。
Objectives: 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 genetic mutations that lead to these phenotypes are random, the process by which some of these mutations become successful and cells spread is influenced by tumour microenvironment and the presence of other cell phenotypes. It is thus likely that some phenotypes that are essential in tumour progression will emerge in the tumour population only with prior presence of other different phenotypes. Materials and methods: In this study, 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 us to understand certain specific aspects of glioma progression such as the emergence of diffuse tumour cell invasion in low-grade tumours. Results: We have found that the invasive phenotype is more likely to evolve after appearance of the glycolytic phenotype which would explain the ubiquitous presence of invasive growth in malignant tumours. Conclusions: The result suggests that therapies, which increase the fitness cost of switching to anaerobic glycolysis, might decrease probability of the emergence of more invasive phenotypes.