The Role of Cell Motility in Metastatic Cell Dominance Phenomenon: Analysis by a Mathematical Model

Abstract

Metastasis is the outcome of several selective sequential steps where one of the first and necessary steps is the progressive overgrowth or dominance of a small number of metastatic cells in a tumour. In spite of numerous experimental investigations concerning the growth advantage of metastatic cells, the mechanisms resulting in their dominance are still unknown. Metastatic cell overgrowth occurs even if doubling time of the metastatic subpopulation is shorter than that of all others subpopulations in a heterogeneous tumour. In order to examine the hypothesis that under conditions of competition of cell subpopulations for common substrata cell motility of the slow-growing subpopulation can result in its dominance in a heterogeneous tumour, a mathematical model of heterogeneous tumour growth is suggested. The model describes two cell subpopulations which can grow with different rates and transform into the resting state depending on the concentration of the substrate consumed by both subpopulations. The slow-growing subpopulation is assumed to be motile. In numerical simulations it is shown that this subpopulation is able to overgrow the other one. The dominance phenomenon (resulting from random cell motion) depends on the motility coefficient in a threshold manner: in a heterogeneous tumour the slow-dividing motile subpopulation is able to overgrow its non-motile counterparts if its motility coefficient exceeds a certain threshold value. Computations demonstrate independence of the motile cells overgrowth from the initial tumour composition.