The Role of Remodeling of the Extracellular Matrix (ECM) in Breast Cancer Progression: The mammary ECM is made up of a complex mesh of proteins, primarily collagen, which is maintained by fibroblast cells. These fibroblast cells create and breakdown tissue as needed, and apply tension on the mesh to protect other cells. Fibroblasts also use the ECM to send mechanical cues to mammary epithelial cells (MECs) in order to maintain a normal equilibrium, or homeostasis. In cancer, this homeostasis is no longer maintained. We predict that these mechanical cues play a significant role in the growth of breast cancer. We found evidence of this in MEC cultures created with and without fibroblasts, where the size and shape of MEC organoids were influenced by fibroblast density. Our laboratory has previously investigated methods of determining the elastic properties of breast tissue by monitoring mechanical waves as the propagate through tissue phantoms (Li et al, 2011; Mohan et al, 2012). Recently, we have developed Diffusion-Sensitive Optical Coherence Tomography (DS-OCT) to explore the nanoporosity of tissue (Blackmon et al, 2016).

DS-OCT is a minimally-invasive imaging technique that measures the rate at which GNRs diffuse through live tissue. GNRs are particularly well suited to study the ECM due to their unique polarization-dependent optical properties. The diffusion rate of the GNRs is sensitive to both viscosity of liquids (Chhetri et al, 2013) and nanoporosity of tissue, such as collagen density (Blackmon et al, 2016) or mucus concentration (Chhetri et al, 2014). Therefore, GNR diffusion can be used as a measure of ECM remodeling by sensing changes in nanoporosity. This is shown in Figure 1(a), where the rate of GNR diffusion decreases as the pore sizes of collagen decrease at higher concentrations.