Computational model of breast cancer cell invasion: exploring the EGF/CSF-1 paracrine signaling between macrophages and tumor cells

Macrophages have been shown, experimentally, to be directly involved in the invasion of breast tumor cells into surrounding tissues and blood vessels. Tumor cells interact with macrophages via a short-ranged signaling pathway involving the epidermal growth factor, EGF, and colony-stimulating factor 1, CSF-1. To study this signaling pathway and the observed motility behaviour of tumor cells I developed a 3D individual cell based computational model. Simulations with my model successfully reproduced results from in vitro and in vivo experiments. The model can help explain mechanisms responsible for the observed motility behaviour of tumor cells and the noted ratio of 3 invasive tumor cells per 1 invasive macrophage. A parametric sensitivity analysis showed that changing model parameters such as the degradation and secretion of EGF and CSF-1 could alter and even eliminate the invasion of tumor cells. These results yield insight into possible new targets for chemotherapy.