Designing a tunable 3D heterocellular breast cancer tissue test system.

It is increasingly recognized that the tissue microenvironment is crucial in cell signaling and regulation of normal and malignant cell function. Components and properties of the microenvironment such as extracellular matrix, adhesion integrins, tissue architectures and tissue modulus regulate growth, differentiation and apoptosis of cells. These properties control cell fate through complex signals that are influenced either by interactions between neighbouring cells or by stimulated cell surface receptors. In this study, we established an in vitro engineered microenvironment: i.e., a tissue test system that combined heterocellular tumour spheroids, polymeric microcarriers and adipocytes, an abundant stromal cell type in breast tissue, to investigate the behaviour of breast cancer cells in response to different environmental stimuli in a more relevant 3D microenvironment. Results showed the engineered microenvironment influenced breast cancer cell proliferation, differentiation and migration through multi-cellular interactions and changes in microenvironmental stiffness and that stromal cells such as adipocytes play a critical role in the breast cancer process.