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生物資訊

腫瘤亞克隆相互作用

作者:admin 來源:2014年7月30日的《Nature》雜 發(fā)布時間: 2014-10-09 08:51  瀏覽次數(shù):
購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.fzy888.com
IL11在腫瘤微環(huán)境上的影響

IL11在腫瘤微環(huán)境上的影響

腫瘤經(jīng)常由在基因損傷和生物性質(zhì)上都不同的細胞群組成,但這種“亞克隆”異質(zhì)性是怎樣出現(xiàn)的以及它對癌癥病情發(fā)展的后果是什么仍然比較模糊。

現(xiàn)在,Kornelia Polyak及同事利用一個小鼠模型發(fā)現(xiàn),腫瘤生長可以由一個小的細胞子類群通過一個非細胞自主機制(non-cell-autonomous mechanism)來驅(qū)動。然而,這一小的細胞子類群也可被更快的增殖競爭對手超越,導致腫瘤瓦解。這些結(jié)果顯示了異質(zhì)腫瘤中亞克隆相互作用和克隆干涉的復雜性,對于治療也有潛在的意義。

原文摘要:

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

Andriy Marusyk, Doris P. Tabassum, Philipp M. Altrock, Vanessa Almendro, Franziska Michor & Kornelia Polyak

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.

 

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