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

dc.contributor.authorPackeiser, Eva-Maria
dc.contributor.authorTaher, Leila
dc.contributor.authorKong, Weibo
dc.contributor.authorErnst, Matthias
dc.contributor.authorBeck, Julia
dc.contributor.authorHewicker-Trautwein, Marion
dc.contributor.authorBrenig, Bertram
dc.contributor.authorSchütz, Ekkehard
dc.contributor.authorEscobar, Hugo Murua
dc.contributor.authorNolte, Ingo
dc.date.accessioned2023-02-10
dc.date.available2023-02-09
dc.date.created2022
dc.date.issued2023-02-10
dc.description.abstractBackground 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 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. Conclusion 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.en
dc.identifier.citationCancer Cell International 22 (2022): 54. <https://cancerci.biomedcentral.com/articles/10.1186/s12935-021-02422-9>
dc.identifier.doihttps://doi.org/10.1186/s12935-021-02422-9
dc.identifier.opus-id21658
dc.identifier.urihttps://open.fau.de/handle/openfau/21658
dc.identifier.urnurn:nbn:de:bvb:29-opus4-216583
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectProstate cancer
dc.subjectMetastasis
dc.subjectBladder cancer
dc.subjectTCC
dc.subjectCell line
dc.subjectDog
dc.subjectGene expression
dc.subjectIn vitro model
dc.subjectTargeted therapy
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleRNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signaturesen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.document.articlenumber54
local.journal.titleCancer Cell International
local.journal.volume22
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.sammlungUniversität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2022
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