Proteomics of cell-free patient-derived scaffolds from breast cancer identify clinically relevant imprinted proteins and cancer-progressing properties

Breast cancer is a heterogenous disease that is difficult to model in vitro. Frozen primary breast cancers were decellularised to generate patient-derived scaffolds which are used to model 3D growth for cancer cell lines. The cell-free cancer microenvironments in the patient-derived scaffolds influence breast cancer cell line phenotypes and enrich for cells with cancer stem cell characteristics. Growth in patient-derived scaffold cultures also influenced the expression of epithelial-to-mesenchymal transition-related genes, and several gene expression changes in the model could be associated to clinical parameters of the original tumors and corresponding patients. Previous studies also demonstrated that the relative protein composition in the cell-free cancers were related to tumor grade and proliferation in cancer cells, suggesting that the relative proteomic composition varies between individual microenvironments. Therefore, we decellularised a larger breast cancer cohort to better characterize the cell-free microenvironments and potentially link to clinical features of the tumors and patients, which could be used to identify novel processes and targets that could be used to better model the disease or targeted in drug discovery.