CREEC/MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier, Cedex 5, France.
Unité mixte internationale de Modélisation Mathématique et Informatique des Systèmes Complexes. (UMI IRD/UPMC UMMISCO), 32 Avenue Henri Varagnat, 93143, Bondy Cedex, France.
Sci Rep. 2017 Sep 11;7(1):11157. doi: 10.1038/s41598-017-11562-w.
Recent cancer research has investigated the possibility that non-cell-autonomous (NCA) driving tumor growth can support clonal diversity (CD). Indeed, mutations can affect the phenotypes not only of their carriers ("cell-autonomous", CA effects), but also sometimes of other cells (NCA effects). However, models that have investigated this phenomenon have only considered a restricted number of clones. Here, we designed an individual-based model of tumor evolution, where clones grow and mutate to yield new clones, among which a given frequency have NCA effects on other clones' growth. Unlike previously observed for smaller assemblages, most of our simulations yield lower CD with high frequency of mutations with NCA effects. Owing to NCA effects increasing competition in the tumor, clones being already dominant are more likely to stay dominant, and emergent clones not to thrive. These results may help personalized medicine to predict intratumor heterogeneity across different cancer types for which frequency of NCA effects could be quantified.
最近的癌症研究调查了非细胞自主（NCA）驱动肿瘤生长是否能够支持克隆多样性（CD）。事实上，突变不仅可以影响其载体的表型（“细胞自主”，CA 效应），有时还可以影响其他细胞的表型（NCA 效应）。然而，研究这一现象的模型只考虑了有限数量的克隆。在这里，我们设计了一个基于个体的肿瘤进化模型，其中克隆生长和突变产生新的克隆，其中给定频率的克隆对其他克隆的生长具有 NCA 效应。与之前观察到的较小集合不同，我们的大多数模拟结果表明，随着 NCA 效应突变频率的增加，CD 会降低。由于 NCA 效应增加了肿瘤内的竞争，已经占主导地位的克隆更有可能保持主导地位，而新兴的克隆则不太可能茁壮成长。这些结果可能有助于个性化医学预测不同癌症类型的肿瘤内异质性，其中可以量化 NCA 效应的频率。
