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| Status |
Public on Feb 08, 2022 |
| Title |
RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures |
| Organism |
Canis lupus familiaris |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Background: 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 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.
Methods: This 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.
Results: Independent analyses for PAC, PAC metastasis and TCC revealed 1,743, 3,941 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.
Conclusions: Comparative 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.
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| Overall design |
Characterization of nine canine prostate cancer cell lines, compared with original tumor tissues
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| Contributor(s) |
Packeiser E, Taher L, Kong W, Ernst M, Beck J, Hewicker-Trautwein M, Brenig B, Schütz E, Murua Escobar H, Nolte I |
| Citation(s) |
35109825 |
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| Submission date |
Dec 07, 2021 |
| Last update date |
Feb 09, 2022 |
| Contact name |
Leila Taher |
| Organization name |
Graz University of Technology
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| Street address |
Stremayrgasse 16/I
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| City |
Graz |
| ZIP/Postal code |
8010 |
| Country |
Austria |
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| Platforms (1) |
| GPL21400 |
Illumina NextSeq 500 (Canis lupus familiaris) |
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| Samples (124)
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| Relations |
| BioProject |
PRJNA786902 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190374_RAW.tar |
60.4 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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