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arXiv 0704.2132q-bio.CBq-bio.QM
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肿瘤细胞克隆体外生长变异性的定量研究

A quantitative study on the growth variability of tumour cell clones in vitro

C. Tomelleri, E. Milotti, C. Dalla Pellegrina, O. Perbellini, A. Del Fabbro, M. T. Scupoli, R. Chignola

摘要:

目的:在这项研究中,我们量化的肿瘤细胞克隆从人白血病细胞系的生长变异性。材料与方法:我们已经使用微孔板分光光度法来测量来自Molt 3细胞系的数百个单个细胞克隆的生长动力学。用Logistic方程拟合实验数据,估算了各无性系种群的生长速率。结果:不同克隆的生长速率不同。最多6个生长速率高于或低于亲本群体平均生长速率的克隆被进一步克隆,并测量其后代的生长速率。亚克隆的生长速率的分布与亲本群体没有显着差异,因此表明生长变异性具有表观遗传起源。为了解释所观察到的克隆生长率的分布,我们已经开发了一个概率模型,假设通过连续的细胞周期的线粒体数量的波动是生长变异性的主要原因。为了拟合的目的,我们通过流式细胞术实验估计了Molt 3细胞中线粒体的最大平均数。该模型很好地拟合了观察到的生长速率分布,然而,其中线粒体被赋予非功能性的细胞(rho-0细胞)相对于正常细胞仅显示克隆生长变异性降低30%。结论:肿瘤细胞群体是具有高度可变生长速率的动态克隆集合。这种变异性至少有一部分是由于线粒体数量的波动。

英文摘要:

Objectives: In this study, we quantify the growth variability of tumour cell clones from a human leukemia cell line. Materials and methods: We have used microplate spectrophotometry to measure the growth kinetics of hundreds of individual cell clones from the Molt3 cell line. The growth rate of each clonal population has been estimated by fitting experimental data with the logistic equation. Results: The growth rates were observed to vary among different clones. Up to six clones with a growth rate above or below the mean growth rate of the parent population were further cloned and the growth rates of their offsprings were measured. The distribution of the growth rates of the subclones did not significantly differ from that of the parent population thus suggesting that growth variability has an epigenetic origin. To explain the observed distributions of clonal growth rates we have developed a probabilistic model assuming that the fluctuations in the number of mitochondria through successive cell cycles are the leading cause of growth variability. For fitting purposes, we have estimated experimentally by flow cytometry the maximum average number of mitochondria in Molt3 cells. The model fits nicely the observed distributions of growth rates, however, cells in which the mitochondria were rendered non functional (rho-0 cells) showed only a 30% reduction in the clonal growth variability with respect to normal cells. Conclusions: A tumor cell population is a dynamic ensemble of clones with highly variable growth rate. At least part of this variability is due to fluctuations in the number of mitochondria.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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