Establishment and characterization of a 3D mamma carcinoma test system on a decellularized scaffold

Breast cancer is the most frequent cancer among women and the second most common cause of cancer death in developed countries. As chemotherapy is often ineffective and causes severe side effects, there is an urgent need for tumor model systems that allow for reliable predictions in drug sensitivity. In this study, we established a 3D mamma carcinoma test system on the basis of a decellularized scaffold derived from porcine small intestine. Two different breast cancer cell lines (MCF-7, MDA-MB-231) were separately cultured on this scaffold under static conditions in a cell crown or under dynamic conditions in a bioreactor for 14 days with or without treatment and afterwards analyzed by immunohistochemistry. The breast cancer cell lines MDA-MB-231 and MCF-7 are reported to be highly invasive and non-invasive, respectively. By using these cell lines, different stages of tumor progression could be modeled in order to investigate their sensitivity towards different therapeutic strategies. Our 3D models showed in vivo-like proliferation rates and the constant medium flow in the bioreactor system allowed the generation of models with higher cell densities and a more tumor-like morphology. With the help of our test system, different therapeutic approaches and their influence on signaling pathways can be investigated. In the future, data from this model will be integrated into a breast cancer-tailored in silico Boolean model, a tool for prediction of drug sensitivity according to mutational background. Our models aim to contribute to the development of personalized treatment based on signaling analysis in different mutational backgrounds and tumor stages, which will improve the selection of patients for the most suitable therapy.