| Autor: |
Schrom S; Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria., Kleinegger F; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria., Anders I; Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria., Hebesberger T; Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria., Karner C; Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria., Liesinger L; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria.; BiotechMed-Graz, 8010 Graz, Austria.; Institute of Chemical Technologies and Analytics, Faculty of Technical Chemistry, Technische Universität Wien, 1060 Vienna, Austria., Birner-Gruenberger R; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria.; BiotechMed-Graz, 8010 Graz, Austria.; Institute of Chemical Technologies and Analytics, Faculty of Technical Chemistry, Technische Universität Wien, 1060 Vienna, Austria., Renner W; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria., Pichler M; BiotechMed-Graz, 8010 Graz, Austria.; Translational Oncology Department, University Hospital of Augsburg, 86156 Augsburg, Germany., Grillari R; Evercyte GmbH, 1190 Vienna, Austria.; Institute of Bioprocess Science and Engineering, University of Natural Resources and Life Sciences-BOKU Wien, 1180 Vienna, Austria., Aigelsreiter A; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria., Rinner B; Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria.; BiotechMed-Graz, 8010 Graz, Austria. |
| Abstrakt: |
Cholangiocarcinoma (CCA) are characterized by their desmoplastic and hypervascularized tumor microenvironment (TME), which is mainly composed of tumor cells and cancer-associated fibroblasts (CAFs). CAFs play a pivotal role in general and CCA tumor progression, angiogenesis, metastasis, and the development of treatment resistance. To our knowledge, no continuous human in vivo-like co-culture model is available for research. Therefore, we aimed to establish a new model system (called MUG CCArly) that mimics the desmoplastic microenvironment typically seen in CCA. Proteomic data comparing the new CCA tumor cell line with our co-culture tumor model (CCTM) indicated a higher gene expression correlation of the CCTM with physiological CCA characteristics. A pro-angiogenic TME that is typically observed in CCA could also be better simulated in the CCTM group. Further analysis of secreted proteins revealed CAFs to be the main source of these angiogenic factors. Our CCTM MUG CCArly represents a new, reproducible, and easy-to-handle 3D CCA model for preclinical studies focusing on CCA-stromal crosstalk, tumor angiogenesis, and invasion, as well as the immunosuppressive microenvironment and the involvement of CAFs in the way that drug resistance develops. |
