Zhou Joseph Xu, Pisco Angela Oliveira, Qian Hong, Huang Sui
Institute for Systems Biology, Seattle, Washington, United States of America; Kavli Institute for Theoretical Physics, University of California Santa Barbara, Santa Barbara, California, United States of America; Institute for Biocomplexity and Informatics, University of Calgary, Calgary, Alberta, Canada.
Institute for Systems Biology, Seattle, Washington, United States of America; Systems Biology Program, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
PLoS One. 2014 Dec 1;9(12):e110714. doi: 10.1371/journal.pone.0110714. eCollection 2014.
Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection) or by environment-instructed transitions (Lamarckism induction). This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.
肿瘤发生是一个动态生物学过程,涉及不同癌细胞亚群以不同速率增殖并在它们之间相互转化。在本文中,我们提出了一个种群动力学的数学框架,该框架考虑了癌细胞群体之间独特的生长速率和细胞间转变。我们的数学框架表明,生长和转变都会影响癌细胞亚群的比例,但后者更为显著。我们推导出了不同癌细胞类型能够维持独特亚群的条件,并且我们还解释了为什么基于假定的表面标志物进行细胞分选后总是存在一个稳定的固定比例。细胞分数比可以通过改变亚群的生长速率(达尔文主义选择)或通过环境诱导的转变(拉马克主义诱导)来改变。这一见解有助于我们理解癌细胞异质性的动力学,并引导我们找到克服癌症耐药性的新策略。