Modeling breast cancer progression in 4-D

Abstract

Cell culture is among the most utilized techniques in biomedical research. The ability to grow mammalian cells in a dish has provided researchers with a tool to study the many mechanisms of biological function. The in vivo interactions in which cells participate, such as extracellular matrix adhesion, breakdown and deposition, along with cell to cell communications are key processes that need to be understood. Three-dimensional (3-D) cell culture has proved amenable to analysis of these interactions. Therefore, we have established a 3-D culture system, which utilizes co-culture of human breast epithelial cells with tumor-associated cells such as macrophages and/or fibroblasts. This unique 3-D model, which we have designated Mammary Architecture and Microenvironment Engineering or MAME, allows us to examine cellular function and mechanisms in a context more comparable to the in vivo microenvironment. In addition, we are able to visualize dynamic cellular processes such as proteolysis and invasion as they occur over time. In this manner we have taken cell cultures from 2-D to a multifaceted 4-D setting.