Hybrid Discrete-Continuum Cellular Automaton (HCA) model of Prostate to Bone Metastasis

Abstract

AbstractProstate to bone metastases induce a “vicious cycle” by promoting excessive osteoclast and osteoblast mediated bone degradation and formation that in turn yields factors that drive cancer growth. Recent advances defining the molecular mechanisms that control the vicious cycle have revealed new therapeutic targeting opportunities. However, given the complex temporal and simultaneous cellular interactions occurring in the bone microenvironment, assessing the impact of putative therapies is challenging. To this end, we have integrated biological and computational approaches to generate an accurate model of normal bone matrix homeostasis and the prostate cancer-bone microenvironment. The model faithfully reproduces the basic multicellular unit (BMU) bone coupling process and introduction of a single prostate cancer cell yields a vicious cycle that is similar in cellular composition and pathophysiology to models of prostate to bone metastasis.