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    Proteomic analysis of extracellular vesicles derived from canine mammary tumour cell lines identifies protein signatures specific for disease state (2024)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Gutierrez-Riquelme, Tania (WE 3)
    Karkossa, Isabel
    Schubert, Kristin
    Liebscher, Gudrun
    Packeiser, Eva-Maria
    Nolte, Ingo
    von Bergen, Martin
    Murua Escobar, Hugo
    Aguilera-Rojas, Matias
    Einspanier, Ralf (WE 3)
    Stein, Torsten (WE 3)
    Quelle
    BMC veterinary research
    Bandzählung: 20
    Heftzählung: 1
    Seiten: 488
    ISSN: 1746-6148
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-024-04331-1
    DOI: 10.1186/s12917-024-04331-1
    Pubmed: 39462388
    Kontakt
    Institut für Veterinär-Biochemie

    Oertzenweg 19 b
    14163 Berlin
    +49 30 838 62225
    biochemie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Background

    Canine mammary tumours (CMT) are among the most common types of tumours in female dogs. Diagnosis currently requires invasive tissue biopsies and histological analysis. Tumour cells shed extracellular vesicles (EVs) containing RNAs and proteins with potential for liquid biopsy diagnostics. We aimed to identify CMT subtype-specific proteome profiles by comparing the proteomes of EVs isolated from epithelial cell lines derived from morphologically normal canine mammary tissue, adenomas, and carcinomas.

    Methods

    Whole-cell protein lysates (WCLs) and EV-lysates were obtained from five canine mammary cell lines: MTH53A (non-neoplastic); ZMTH3 (adenoma); MTH52C (simple carcinoma); 1305, DT1406TB (complex carcinoma); and their proteins identified by LC-MS/MS analyses. Gene Ontology analysis was performed on differentially abundant proteins from each group to identify up- and down-regulated biological processes. To establish CMT subtype-specific proteomic profiles, weighted gene correlation network analysis (WGCNA) was carried out.

    Results

    WCL and EVs displayed distinct protein abundance signatures while still showing the same increase in adhesion, migration, and motility-related proteins in carcinoma-derived cell lines, and of RNA processing and RNA splicing factors in the adenoma cell line. WGCNA identified CMT stage-specific co-abundant EV proteins, allowing the identification of adenoma and carcinoma EV signatures not seen in WCLs.

    Conclusions

    EVs from CMT cell lines exhibit distinct protein profiles reflecting malignancy state, allowing us to identify potential biomarkers for canine mammary carcinomas, such as biglycan. Our dataset could therefore potentially serve as a basis for the development of a less invasive clinical diagnostic tool for the characterisation of CMT.