Non - cell - autonomous driving of tumour growth supports sub-clonal heterogeneity

摘要

Cancers arise through a process of somatic evolution that can result in substantial sub - clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.%肿瘤经常由在基因损伤和生物性质上都不同的细胞群组成，但这种“亚克隆”异质性是怎样出现的以及它对癌症病情发展的后果是什么仍然比较模糊。现在，Kornelia Polyak及同事利用一个小鼠模型发现，肿瘤生长可以由一个小的细胞子类群通过一个非细胞自主机制(non-cell-autonomous mechanism)来驱动。然而，这一小的细胞子类群也可被更快的增殖竞争对手超越，导致肿瘤瓦解。这些结果显示了异质肿痼中亚克隆相互作用和克隆干涉的复杂性，对于治疗也有潜在的意义。