Study of Stroma and Tumor Growth Interaction in Ductal Carcinoma in Situ Progress: A 3D Agent-Based Modeling Approach

Abstract

The transition in breast cancer from ductal carcinoma in situ to invasive ductal carcinoma marks a significant drop in patient survival and is one of the leading causes of death in women. Tumor initiation, growth, and metastasis are primarily driven by multiple biochemical and biomechanical interactions among the epithelia, tumor cells, diffusible signals, and stromal components such as fibroblasts, myofibroblasts and extracellular matrix in the ductal microenvironments. Understanding how the interplay among these components drives the dynamics of metastasis and invasion may lead to new therapeutic approaches to breast cancer. We introduced a 3D multicellular agent-based model of DCIS growth and invasion that includes ductal, stromal and tumor cell types acting along with microenvironmental components such as matrix metalloproteinases (MMP), Lysyl oxidase(LOX), nutrients, TGF\u27 and extracellular matrix (ECM) protein assemblies. We are investigating a wide range of parameters and assumptions in our model that lead to change in the model outcomes. The model explicitly determines mechanical tensional and compressive forces within the developing tissue