Department of Bioinformatics, Matthias Schleiden Institute, Friedrich Schiller University, Ernst-Abbe-Platz 2, 07743, Jena, Germany.
Institute of Zoology and Evolutionary Research, University of Jena, Erbertstr. 1, 07743, Jena, Germany.
Sci Rep. 2023 Oct 5;13(1):16758. doi: 10.1038/s41598-023-43199-3.
A medically important feature of several types of tumors is their ability to "decide" between staying at a primary site in the body or leaving it and forming metastases. The present theoretical study aims to provide a better understanding of the ultimate reasons for this so-called "go-or-grow" dichotomy. To that end, we use game theory, which has proven to be useful in analyzing the competition between tumors and healthy tissues or among different tumor cells. We begin by determining the game types in the Basanta-Hatzikirou-Deutsch model, depending on the parameter values. Thereafter, we suggest and analyze five modified variants of the model. For example, in the basic model, the deadlock game, Prisoner's Dilemma, and hawk-dove game can occur. The modified versions lead to several additional game types, such as battle of the sexes, route-choice, and stag-hunt games. For some game types, all cells are predicted to stay on their original site ("grow phenotype"), while for other types, only a certain fraction stay and the other cells migrate away ("go phenotype"). If the nutrient supply at a distant site is high, all the cells are predicted to go. We discuss our predictions in terms of the pros and cons of caloric restriction and limitations of the supply of vitamins or methionine. Our results may help devise treatments to prevent metastasis.
几种类型的肿瘤具有在体内原发部位停留或离开原发部位形成转移灶的“决策”能力，这是医学上的一个重要特征。本理论研究旨在更好地理解这种所谓的“去或留”二分法的根本原因。为此，我们使用博弈论，博弈论已被证明在分析肿瘤与健康组织之间或不同肿瘤细胞之间的竞争时非常有用。我们首先根据参数值确定 Basanta-Hatzikirou-Deutsch 模型中的博弈类型。此后，我们提出并分析了该模型的五个修改变体。例如，在基本模型中，可能会出现僵局博弈、囚徒困境和鹰鸽博弈。修改后的版本会导致几种额外的博弈类型，如性别之战、路线选择和猎鹿博弈。对于某些博弈类型，所有细胞都被预测停留在原始位置（“生长表型”），而对于其他类型，只有一部分细胞停留，其他细胞迁移（“去表型”）。如果远处部位的营养供应很高，那么所有细胞都被预测会离开。我们根据热量限制的利弊以及维生素或蛋氨酸供应的限制来讨论我们的预测。我们的研究结果可能有助于制定预防转移的治疗方法。
