Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity | |
Article | |
关键词: IL-6 FAMILY CYTOKINE; CANCER; EVOLUTION; MODEL; TUMORIGENESIS; INFLAMMATION; COMPETITION; MUTATIONS; SELECTION; LEUKEMIA; | |
DOI : 10.1038/nature13556 | |
来源: SCIE |
【 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 on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by 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.
【 授权许可】
Free