Tuesday, March 17, 2015

The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity

The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity

The paradigm of phenotypic plasticity indicates reversible relations of different cancer cell phenotypes, which challenges the cellular hierarchy proposed by the conventional cancer stem cell (CSC) theory. Since the validity of the reversible model versus the hierarchical model of cancer cells is still experimentally debated, it is worthwhile to theoretically explore the dynamic behavior characterizing the reversible model in comparison of the hierarchical model. By comparing the two models in predicting the cell-state dynamics observed in biological experiments, our results imply that the reversible model has advantages over the hierarchical model in predicting both long-term stable and short-term transient dynamics of cancer cells. In particular, it is found that i) the reversible model can predict the phenotypic equilibrium better than the hierarchical model, namely, the stability of the phenotypic mixture of cancer cells is more rooted in the reversible model; ii) the reversible model can perform various types of overshoot behavior, whereas the hierarchical model can never predict the overshoot of CSCs proportion. These also indicate that the phenotypic equilibrium and overshoot can be good candidates to characterize the models with the reversible phenotypic plasticity.
http://arxiv.org/abs/1503.04558