A mathematical model with aberrant growth correction in tissue homeostasis and tumor cell growth

摘要

Cancer is usually considered a genetic disease caused by alterations in genes that control cellular behaviors, especially growth and division. Cancer cells differ from normal tissue cells in many ways that allow them to grow out of control and become invasive. However, experiments have shown that aberrant growth in many tissues burdened with varying numbers of mutant cells can be corrected, and wild-type cells are required for the active elimination of mutant cells. These findings reveal the dynamic cellular behaviors that lead to a tissue homeostatic state when faced with mutational and nonmutational insults. The current study was motivated by these observations and established a mathematical model of how a tissue copes with the aberrant behavior of mutant cells. The proposed model depicts the interaction between wild-type and mutant cells through a system of two delay differential equations, which include the random mutation of normal cells and the active extrusion of mutant cells. Based on the proposed model, we performed qualitative analysis to identify the conditions of either normal tissue homeostasis or uncontrolled growth with varying numbers of abnormal mutant cells. Bifurcation analysis suggests the conditions of bistability with either a small or large number of mutant cells, the coexistence of bistable steady states can be clinically beneficial by driving the state of mutant cell predominance to the attraction basin of the state with a low number of mutant cells. This result is further confirmed by the treatment strategy obtained from optimal control theory.