Crosstalk between the extracellular matrix and breast stem cells in health and disease

Female breast development occurs at puberty and undergoes many cyclic changes under normal physiological conditions, like pregnancy, lactation and involution. The breast epithelium is surrounded by a heterogenous stroma that encompasses various cell types, including fibroblasts, immune cells, adipocytes, endothelial cells and an extracellular matrix (ECM). The ECM is a complex molecular meshwork composed of a variety of matricellular proteins and ECM remodelling enzymes, including proteases. Dynamic remodelling of the ECM is fundamental to the organisation and function of the mammary gland and is associated with stemness. It is often aberrantly regulated in breast cancer, which still has the highest incidence and mortality rates in women worldwide. Improved models could contribute to a better understanding of cell-matrix interactions, including in the stem cell niche, and ECM remodelling in health and tumorigenesis. This could lay the groundwork for therapeutic strategies that also target the breast cancer ECM for improved precision medicine tools.