Abstract
Tumor cells develop different strategies to cope with changing microenvironmental conditions. A prominent example is the adaptive phenotypic switching between cell migration and proliferation. While it has been shown that the migration-proliferation plasticity influences tumor spread, it remains unclear how this particular phenotypic plasticity affects overall tumor growth, in particular initiation and persistence. To address this problem, we formulate and study a mathematical model of spatio-temporal tumor dynamics which incorporates the microenvironmental influence through a local cell density dependence. Our analysis reveals that two dynamic regimes can be distinguished. If cell motility is allowed to increase with local cell density, any tumor cell population will persist in time, irrespective of its initial size. On the contrary, if cell motility is assumed to decrease with respect to local cell density, any tumor population below a certain size threshold will eventually extinguish, a fact usually termed as Allee effect in ecology. These results suggest that strategies aimed at modulating migration are worth to be explored as alternatives to those mainly focused at keeping tumor proliferation under control.
Highlights
Tumor cells possess a remarkable phenotypic plasticity that allows for adaptation to changing microenvironmental conditions [1, 2]
Current clinical therapies focus on strategies to reduce tumor cell proliferation
During tumor progression, tumor cells may switch between proliferative and migratory behaviors, thereby allowing adaptation to microenvironmental changes that result in variations in local tumor cell density
Summary
Tumor cells possess a remarkable phenotypic plasticity that allows for adaptation to changing microenvironmental conditions [1, 2]. It has been suggested that the switch between migrating and proliferative phenotypes is dependent on the cells’ microenvironment such as growth factor gradients [7], properties of the extracellular matrix [12] or altered energy availability [13]. In this context, several mathematical models have shown that the migration-proliferation plasticity has a major impact on tumor spread [14,15,16,17,18,19]. While the consequences of density-dependent migration-proliferation plasticity on local tumor spread, as an essential feature of tumor invasion, have been explored already [14, 18, 19], the potential effects of this type of plasticity on tumor initiation and persistence have not been investigated so far
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