TGF-β induces matrisome pathological alterations and EMT in patient-derived prostate cancer tumoroids
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
37944712
DOI
10.1016/j.matbio.2023.11.001
PII: S0945-053X(23)00113-0
Knihovny.cz E-resources
- Keywords
- Cancer, Epithelial-to-mesenchymal transition (EMT), Extracellular matrix (ECM), Prostate, Transforming growth factor (TGF)-β, Tumoroids, Tumour,
- MeSH
- Epithelial-Mesenchymal Transition MeSH
- Extracellular Matrix metabolism MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms * pathology MeSH
- Prostate metabolism MeSH
- Transforming Growth Factor beta * metabolism MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Transforming Growth Factor beta * MeSH
Extracellular matrix (ECM) tumorigenic alterations resulting in high matrix deposition and stiffening are hallmarks of adenocarcinomas and are collectively defined as desmoplasia. Here, we thoroughly analysed primary prostate cancer tissues obtained from numerous patients undergoing radical prostatectomy to highlight reproducible structural changes in the ECM leading to the loss of the glandular architecture. Starting from patient cells, we established prostate cancer tumoroids (PCTs) and demonstrated they require TGF-β signalling pathway activity to preserve phenotypical and structural similarities with the tissue of origin. By modulating TGF-β signalling pathway in PCTs, we unveiled its role in ECM accumulation and remodelling in prostate cancer. We also found that TGF-β-induced ECM remodelling is responsible for the initiation of prostate cell epithelial-to-mesenchymal transition (EMT) and the acquisition of a migratory, invasive phenotype. Our findings highlight the cooperative role of TGF-β signalling and ECM desmoplasia in prompting prostate cell EMT and promoting tumour progression and dissemination.
Department of Computer Engineering Modelling Electronics and Systems Engineering 87036 Italy
Department of Engineering for Innovation University of Salento Italy
Department of Urology St Anne's University Hospital Brno 60200 Czech Republic
Information Technology Center 87036 Italy
International Clinical Research Center St Anne's University Hospital Brno 60200 Czech Republic
References provided by Crossref.org
Regulation of Cell-Nanoparticle Interactions through Mechanobiology
Unraveling the Role of the Tumor Extracellular Matrix to Inform Nanoparticle Design for Nanomedicine
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