LAUSR

Progression from a ductal carcinoma in situ (DCIS) to an invasive tumor is a major step initiating a devastating and often lethal metastatic cascade. One of the first steps in this process is the development of ductal microinvasions, i.e., small cohorts of tumor cells that breach the basement membrane surrounding the duct, and migrate through the extracellular matrix (ECM). At this point, for the first time, the epithelially-derived tumor cells engage in a direct physical contact with the extracellular matrix and the stroma. We combined single cell-based model of the tumor-ECM interactions and ECM remodeling, and image-based analysis of the cellular biophysico-chemical features as determined from patients’ histology samples of DCIS. Using this model we showed how changes in the local microenvironmental niche near the DCIS edge enable initiation and progression of ductal microinvasions. Of particular interest are the biomechanical interactions between the cells and the ECM fiber structure, and microenvironmental features that define niche prone to microinvasions. These findings can be compared to the patient histology samples and help define criteria for future development of new prognostic methods and therapeutic interventions by targeting the tumor niche.