Population dynamics of cancer cells with cell state conversions

作     者：Da Zhou Dingming Wu Zhe Li Minping Qian Michael Q. Zhang 

作者机构：MOE Key Laboratory of Bioinformatics Bioinformatics Division/Center for Synthetic & Systems Biology TNLIST Department of Automation Tsinghua University Beijing 100084 China Computational Neuroscience Lab School of Medicine Tsinghua University Beijing 100084 China School of Mathematical Sciences Peking University Beijing 100871 China Department of Molecular and Cell Biology Center for Systems Biology The University of Texas at Dallas Richardson TX 75080. USA 

出 版 物：《Frontiers of Electrical and Electronic Engineering in China》 (中国电气与电子工程前沿（英文版）)

年 卷 期：2013年第8卷第3期

页      面：201-208页

学科分类：1002[医学-临床医学] 0839[工学-网络空间安全] 08[工学] 100214[医学-肿瘤学] 10[医学] 

基　　金：CPSF, (2012M510402) NBRPC, (2012CB316503) National Institutes of Health, NIH, (ES017166) National Natural Science Foundation of China, NSFC, (31061160497, 91010016) 

主　　题：Breast Cancer Cell Line Cancer Stem Cell Cell State Markov Chain Model Transient Dynamic 

摘      要：Cancer stem cell （CSC） theory suggests a cell-lineage structure in tumor cells in which CSCs are capable of giving rise to the other non-stem cancer cells （NSCCs） but not vice versa. However, an alternative scenario of bidirectional interconversions between CSCs and NSCCs was proposed very recently. Here we present a general population model of cancer cells by integrating conventional cell divisions with direct conversions between different cell states, namely, not only can CSCs differentiate into NSCCs by asymmetric cell division, NSCCs can also dedifferentiate into CSCs by cell state conversion. Our theoretical model is validated when applying the model to recent experimental data. It is also found that the transient increase in CSCs proportion initiated from the purified NSCCs subpopulation cannot be well predicted by the conventional CSC model where the conversion from NSCCs to CSCs is forbidden, implying that the cell state conversion is required especially for the transient dynamics. The theoretical analysis also gives the condition such that our general model can be equivalently reduced into a simple Markov chain with only cell state transitions keeping the same cell proportion dynamics.