Modeling tumor cell shedding.

Cell shedding is an important step in the development of tumor invasion and metastasis. It influences growth saturation, latency, and tumor surface roughness. In spite of careful experiments carried out using multicellular tumor spheroids (MTS), the effects of the shedding process are not yet completely understood. Using a simulational model, we study how the nature and intensity of cell shedding may influence tumor morphology and examine the dependence of the total number of shed cells with the relevant parameters, finding the ranges that maximize cell detachment. These ranges correspond to intermediate values of the adhesion, for which we observe the emergence of a rough tumor surface. They are also likely to maximize the probability of generating invasion and metastases. Using numerical values taken from experiments, we find that the shedding-induced reduction in the growth rate is not intense enough to lead to latency, except when cell adhesion is assumed to be very weak. This suggests that the presence of inhibitors is a necessary condition for the observed MTS growth saturation.