Abstract
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.
Highlights
Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance
Both are typically characterized by metastasis, local invasiveness, androgen-independence and chemoresistance [2, 3], which is why they have been proposed as models for human metastatic castration-resistant prostate cancer (MCRPC) and invasive bladder cancer [4, 5]
Principal component analysis (PCA) of the transcriptomic profiles of all samples clearly distinguished between cell lines and tissue samples (Fig. 2)
Summary
Canine 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 strate‐ gies As they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Prostate cancer in dogs can be classified into two histopathological groups: prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) [1] Both are typically characterized by metastasis, local invasiveness, androgen-independence and chemoresistance [2, 3], which is why they have been proposed as models for human metastatic castration-resistant prostate cancer (MCRPC) and invasive bladder cancer [4, 5]. Canine prostate cancer is rarely diagnosed [6, 7], making tumor cell lines an indispensable in vitro model system and a vital tool in preclinical research [8, 9]. Applications for cell lines as in vitro models are versatile, including research on metastasis, targeted therapy and chemoresistance
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