Abstract: Cancer cells exhibit increased motility and proliferation, which are instrumental in the formation of tumours and metastases. These pathological changes can be traced back to malfunctions of cellular signalling pathways, and calcium signalling plays a prominent role in these. We formulate a new model for cancer cell movement which for the first time explicitly accounts for the dependence of cell proliferation and cell-cell adhesion on calcium. At the heart of our work is a non-linear, integro-differential (non-local) equation for cancer cell movement, accounting for cell diffusion, advection and proliferation. We also employ an established model of cellular calcium signalling with a rich dynamical repertoire that includes experimentally observed periodic wave trains and solitary pulses. The cancer cell density exhibits travelling fronts and complex spatial patterns arising from an adhesion-driven instability (ADI). We show how the different calcium signals and variations in the strengths of cell-cell attraction and repulsion shape the emergent cellular aggregation patterns, which are a key component of the metastatic process. Performing a linear stability analysis, we identify parameter regions corresponding to ADI. These regions are confirmed by numerical simulations, which also reveal different types of aggregation patterns and these patterns are significantly affected by \ca. Our study demonstrates that the maximal cell density decreases with calcium concentration, while the frequencies of the calcium oscillations and the cell density oscillations are approximately equal in many cases. Furthermore, as the calcium levels increase the speed of the travelling fronts increases, which is related to a higher cancer invasion potential. These novel insights provide a step forward in the design of new cancer treatments that may rely on controlling the dynamics of cellular calcium.
This publication is part of the Non-local models of cell-cell adhesion project.