Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems |
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| Authors: | Yi Wei Bastian Amend Tilman Todenhfer Nizar Lipke Wilhelm K Aicher Falko Fend Arnulf Stenzl Niklas Harland |
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| Affiliation: | 1.Center for Medicine Research, Eberhard Karls University, 72072 Tuebingen, Germany; (Y.W.); (N.L.); (W.K.A.);2.Department of Urology, University Hospital, 72076 Tuebingen, Germany; (B.A.); (T.T.); (A.S.);3.Institute for Pathology, Eberhard Karls University, 72076 Tuebingen, Germany; |
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| Abstract: | Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC50 toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies. |
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| Keywords: | bladder cancer drug screening bladder cancer organoids BH3 mimics |
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