Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression.
breast cancer
desmoplasia
extracellular matrix
fibroblasts
mechanics
models
pancreatic cancer
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
01
2023
accepted:
30
05
2023
medline:
7
8
2023
pubmed:
4
8
2023
entrez:
4
8
2023
Statut:
epublish
Résumé
The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies.
Identifiants
pubmed: 37539058
doi: 10.3389/fimmu.2023.1154528
pmc: PMC10395327
doi:
Substances chimiques
Extracellular Matrix Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1154528Informations de copyright
Copyright © 2023 Rafaeva, Jensen, Horton, Zornhagen, Strøbech, Fleischhauer, Mayorca-Guiliani, Nielsen, Grønseth, Kuś, Schoof, Arnes, Koch, Clausen-Schaumann, Izzi, Reuten and Erler.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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