Breast Cancer Patient-Derived Scaffolds Can Expose Unique Individual Cancer Progressing Properties of the Cancer Microenvironment Associated with Clinical Characteristics

SIMPLE SUMMARY: Despite huge progress in cancer diagnostics and medicine we still lack optimal cancer treatments for patients with aggressive diseases. This problem can be influenced by the biological heterogeneity of cancer cells as well as poorly understood cancer promoting effects of the cancer microenvironment being an important part of the cancer niche. In this study we have specifically monitored the activity of the cancer microenvironment in breast cancer patients using cell-free scaffolds repopulated with reporter cancer cells sensing the activity of the patient environment. The data show that scaffold induced changes in epithelial-mesenchymal transition and pluripotency markers were linked to clinical and prognostic properties of the original cancer and the information was even more precise when matching estrogen receptor status in our system. The findings highlight that patient-derived scaffolds uncover important information about varying malignant promoting properties in the cancer niche and can be used as a complementary diagnostic tool. ABSTRACT: Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established in vivo-like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ERα-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.