Tumor cells interact with the microenvironment that specifically supports and promotes
tumor development. Key components in the
tumor environment have been linked to various aggressive
cancer features and can further influence the presence of subpopulations of
cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast
cancers infiltrated with standardized
breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the
cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their
protein composition that were linked to clinical properties, including
tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in
cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in
breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the
malignancy-inducing properties of tumor microenvironment.