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| Status |
Public on Nov 22, 2023 |
| Title |
TGF-β induces matrisome pathological alterations and EMT in patient-derived prostate cancer tumoroids |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Comparative gene expression analysis of RNA-seq data obtained from prostate cancer organoids treated in the presence or absence of TGF-B signalling pathway inhibitor (A-83-01). Organoids isolated from 5 different donors were used for this study.
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| Web link |
https://doi.org/10.1016/j.matbio.2023.11.001
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| Contributor(s) |
Fernandes S, Oliver-De La Cruz J, Cassani M, Morazzo S, Ďuríková H, Caravella A, Fiore P, Azzato G, De Marco G, Lauria A, Izzi V, Bosáková V, Fric J, Filipensky P, Forte G, Hejret V |
| Citation(s) |
37944712 |
| Submission date |
Apr 18, 2023 |
| Last update date |
Nov 23, 2023 |
| Contact name |
Philipp Arnold |
| E-mail(s) |
philipp.arnold@fau.de
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| Organization name |
Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität Erlangen-Nürnberg
|
| Street address |
Universitätsstraße 19
|
| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (10)
|
| GSM7182698 |
Patient 32 organoids treated with TGF-B signalling pathway inhibitor A 83-01 |
| GSM7182699 |
Patient 33 organoids treated with TGF-B signalling pathway inhibitor A 83-01 |
| GSM7182700 |
Patient 35 organoids treated with TGF-B signalling pathway inhibitor A 83-01 |
| GSM7182701 |
Patient 36 organoids treated with TGF-B signalling pathway inhibitor A 83-01 |
| GSM7182702 |
Patient 37 organoids treated with TGF-B signalling pathway inhibitor A 83-01 |
| GSM7182703 |
Patient 32 organoids control |
| GSM7182704 |
Patient 33 organoids control |
| GSM7182705 |
Patient 35 organoids control |
| GSM7182706 |
Patient 36 organoids control |
| GSM7182707 |
Patient 37 organoids control |
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| Relations |
| BioProject |
PRJNA956959 |
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