A spatiotemporal model for tumour growth driven by stem cells

J. RIVERA; R.A. RAMOS; C.A. CONDAT

Cusco

Congreso; X Congreso Latinoamericano de Biología Matemática (SOLABIMA 17); 2017

Sociedad Latinoamericana de Biomatemática

There is growing evidence that cancer growth is often driven by cancer stem cells. These cells, whose behavior is strongly influenced by the local environment, may have the ability to escape cytotoxic therapy and are thus likely to be responsible for the emergence of resistance. We have developed a simulation model for the cancer stem cell mediated growth of solid tumors. We implement it by considering a lattice in whose nodes reside five competing cell populations: healthy cells, differentiated cancer cells, cycling cancer stem cells, quiescent cancer stem cells, and dead cells. Cell differentiation, mitosis and death are assumed to be regulated by cell concentrations in neighboring nodes. For instance, quiescent cancer stem cells can divide symmetrically into two differentiated cancer cells when the average cancer cell density in their neighborhood exceeds a threshold U. Reentrance of quiescent cancer stem cells into the cell cycle is triggered when enough noncancerous cells are registered in the neighborhood. When a cycling cancer stem cell replicates, it yields two initially quiescent cancer stem cells. Differentiated cancer cells may proliferate or die. Starting with a cancer stem cell seed, we observe how the tumor evolves in such a way that most cancer stem cells end up in the periphery, while the interior is mostly occupied by differentiated cancer cells. After a time, a necrotic core emerges in the central zone. We investigate how the system evolution depends on the relevant parameters, such as the threshold U, the differentiation rate of the quiescent cancer stem cells, and the rate of reentrance of quiescent cells into the cycle. We also explore the conditions for the success of a differentiation therapy, in which a differentiating agent, such as retinoid acid, diffuses from the vascular system and is absorbed by the cancer stem cells, inducing their differentiation when the local concentration of the differentiating agent reaches a threshold.