Tracing the dynamics of mammary tumor initiation.

Breast cancer is the most commonly occurring cancer in women worldwide. Based on gene expression, breast tumors can be further subdivided into five main molecular subtypes (Luminal A, Luminal B, Her2+, Triple-negative, and Normal-like). Each of these tumor types originates in the ductal epithelium of the breast, however, the cell type(s) in which each of these breast tumor subtypes originate remains unknown. Moreover, it is unclear whether specific parts of the ductal epithelium are more or less prone to tumor initiation and progression. To unravel the location and cell-of-origin of breast cancer, we will make use of a combination of genetically engineered fluorescent mouse models and high-end (intravital) microscopy techniques. Using these mouse models, we aim to follow the initial steps of tumorigenesis in the mammary gland at a single-cell level. To this end, we will make use of surgically implanted imaging windows that obtain optical access to the mammary gland. The use of these imaging windows in combination with intravital microscopy will enable us to follow the dynamics of tumor initiation within the mammary gland over multiple days to weeks. By visualizing the dynamic behavior of pre-malignant tumor cells, we hope to unveil the location as well as the cells in which mammary tumors originate.