Abstract P1-04-01: Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment

Despite great efficiencies of today’s anti-cancer therapies in breast cancer medicine, recurrences and metastasis still remains a major challenge. The tumor initiating population of cancer stem cells (CSC) is believed to promote metastasis and drug resistance, suggesting that selectively targeting CSC and their niche may be a potential beneficial therapeutic strategy. However, specific driving factors in the microenvironment influencing the CSC niche remains unknown. To study the influence of specific cancer microenvironments, we have developed a novel three-dimensional cell culture platform, using cell-free patient derived scaffolds (PDS) from decellularized breast cancer tumors. We confirmed that our novel patient derived scaffold (PDS) recapitulates the native microenvironment where the cancer cells originate and, retains their biological properties. Our data demonstrate that culturing breast cancer cell lines in PDSs promotes CSC and EMT-like properties and decreases proliferation, similarly to in vivo conditions. Additionally, global gene expression profiling revealed that PDS cultures exhibit transcriptional patterns more similar to patient derived xenografts than to traditional monolayer cultures. Moreover, we analyzed the expression of cells cultured in 108 PDSs made from breast cancer tumors with clinical follow-up data, using a gene panel representative of relevant breast cancer related processes. This revealed that expression changes of several EMT markers and other CSC related genes in the PDS cultured cancer cells were correlated to clinical parameters such as grade, lymph node metastasis, patient survival and disease recurrences. Altogether, our data shows that PDS can reveal unique additional information about the malignancy-inducing properties of specific tumor microenvironments, potentially provides a complementary diagnosis tool for breast cancer tumors in vitro, and is a promising platform for drug screening of anti-cancer therapies. Citation Format: Elena Garre, Anna Gustafsson, Maria del Carmen Leiva-Arrabal, Paul Fitzpatrick, Pernilla Gregersson, Anders Stahlberg, Goran Landberg. Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-01.