Cancer-Associated Fibroblasts in a 3D Engineered Tissue Model Induce Tumor-like Matrix Stiffening and EMT Transition.
3D tumor models
ECM remodeling
EMT
bladder cancer
cancer-associated fibroblasts
cell contractility
engineered tumor microenvironment
matrix stiffness
mechanotransduction
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
05 Aug 2022
05 Aug 2022
Historique:
received:
07
07
2022
revised:
30
07
2022
accepted:
01
08
2022
entrez:
12
8
2022
pubmed:
13
8
2022
medline:
13
8
2022
Statut:
epublish
Résumé
A tumor microenvironment is characterized by its altered mechanical properties. However, most models remain unable to faithfully recreate the mechanical properties of a tumor. Engineered models based on the self-assembly method have the potential to better recapitulate the stroma architecture and composition. Here, we used the self-assembly method based on a bladder tissue model to engineer a tumor-like environment. The tissue-engineered tumor models were reconstituted from stroma-derived healthy primary fibroblasts (HFs) induced into cancer-associated fibroblast cells (iCAFs) along with an urothelium overlay. The iCAFs-derived extracellular matrix (ECM) composition was found to be stiffer, with increased ECM deposition and remodeling. The urothelial cells overlaid on the iCAFs-derived ECM were more contractile, as measured by quantitative polarization microscopy, and displayed increased YAP nuclear translocation. We further showed that the proliferation and expression of epithelial-to-mesenchymal transition (EMT) marker in the urothelial cells correlate with the increased stiffness of the iCAFs-derived ECM. Our data showed an increased expression of EMT markers within the urothelium on the iCAFs-derived ECM. Together, our results demonstrate that our tissue-engineered tumor model can achieve stiffness levels comparable to that of a bladder tumor, while triggering a tumor-like response from the urothelium.
Identifiants
pubmed: 35954473
pii: cancers14153810
doi: 10.3390/cancers14153810
pmc: PMC9367573
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : CIHR
ID : 258229
Pays : Canada
Organisme : Fondation de l'Université Laval
ID : N/A
Organisme : Canada Research Chairs
ID : N/A
Organisme : Ferring Canada
ID : N/A
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