Basanta D, Simon M, Hatzikirou H, Deutsch A
Zentrum für Informationsdienste und Hochleistungsrechnen, Technische Universität Dresden, Dresden, Germany, andNeurochirurgische Universitätsklinik, Universität Bonn, Bonn, Germany.
Cell Prolif. 2008 Dec;41(6):980-987. doi: 10.1111/j.1365-2184.2008.00563.x.
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.
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.
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.
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.
肿瘤进展被描述为一系列特征或表型，如果肿瘤要发展成为侵袭性和恶性癌症，细胞就必须获得这些特征或表型。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以及细胞扩散的过程会受到肿瘤微环境和其他细胞表型的影响。因此，一些在肿瘤进展中至关重要的表型可能只有在肿瘤群体中预先存在其他不同表型的情况下才会出现。
在本研究中，我们使用进化博弈论来分析由自主生长、无氧糖酵解和癌细胞侵袭所定义的三种不同肿瘤细胞表型之间的相互作用。该模型使我们能够理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。
我们发现，侵袭性表型在糖酵解表型出现后更有可能进化，这可以解释恶性肿瘤中侵袭性生长的普遍存在。
该结果表明，增加转向无氧糖酵解的适应性成本的疗法可能会降低更具侵袭性表型出现的概率。
