RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures

Cancer Cell International

Julia Beck¹  Ekkehard Schütz¹  Marion Hewicker-Trautwein²  Mathias Ernst³  Leila Taher⁴  Ingo Nolte⁵  Eva-Maria Packeiser⁶  Hugo Murua Escobar⁷  Weibo Kong⁸  Bertram Brenig⁹ 

[1] Chronix Biomedical, Göttingen, Germany;Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany;Division of Bioinformatics, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany;Institute of Biomedical Informatics, Graz University of Technology, Graz, Austria;Division of Bioinformatics, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany;Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, 18057, Rostock, Germany;Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany;Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany;Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, Rostock, Germany;Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany;Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, Rostock, Germany;Comprehensive Cancer Center Mecklenburg-Vorpommern (CCC-MV), Campus Rostock, University of Rostock, 18057, Rostock, Germany;Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany;Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, Rostock, Germany;Institute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany;University of Göttingen, Institute of Veterinary Medicine, Göttingen, Germany;

关键词: Prostate cancer;    Metastasis;    Bladder cancer;    TCC;    Cell line;    Dog;    Gene expression;    In vitro model;    Targeted therapy;   

DOI  :  10.1186/s12935-021-02422-9

来源: Springer

【 摘 要 】

BackgroundCanine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance. Cell lines are important model systems for developing new therapeutic strategies. However, as they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Therefore, a comprehensive characterization of cell lines and their original tissues is paramount.MethodsThis study compared the transcriptomes of nine canine cell lines derived from PAC, PAC metastasis and TCC to their respective original primary tumor or metastasis tissues. Special interests were laid on cell culture-related differences, epithelial to mesenchymal transition (EMT), the prostate and bladder cancer pathways, therapeutic targets in the PI3K-AKT signaling pathway and genes correlated with chemoresistance towards doxorubicin and carboplatin.ResultsIndependent analyses for PAC, PAC metastasis and TCC revealed 1743, 3941 and 463 genes, respectively, differentially expressed in the cell lines relative to their original tissues (DEGs). While genes associated with tumor microenvironment were mostly downregulated in the cell lines, patient-specific EMT features were conserved. Furthermore, examination of the prostate and bladder cancer pathways revealed extensive concordance between cell lines and tissues. Interestingly, all cell lines preserved downstream PI3K-AKT signaling, but each featured a unique therapeutic target signature. Additionally, resistance towards doxorubicin was associated with G2/M cell cycle transition and cell membrane biosynthesis, while carboplatin resistance correlated with histone, m- and tRNA processing.ConclusionComparative whole-transcriptome profiling of cell lines and their original tissues identifies models with conserved therapeutic target expression. Moreover, it is useful for selecting suitable negative controls, i.e., cell lines lacking therapeutic target expression, increasing the transfer efficiency from in vitro to primary neoplasias for new therapeutic protocols. In summary, the dataset presented here constitutes a rich resource for canine prostate and bladder cancer research.

【 授权许可】

CC BY