Fibrotic enzymes modulate wound-induced skin tumorigenesis.
PRSS35
cancer-associated fibroblasts
fibrosis
skin cancer
wound healing
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
revised:
08
02
2021
received:
21
08
2020
accepted:
18
02
2021
pubmed:
30
3
2021
medline:
1
6
2021
entrez:
29
3
2021
Statut:
ppublish
Résumé
Fibroblasts are a major component of the microenvironment of most solid tumours. Recent research elucidated a large heterogeneity and plasticity of activated fibroblasts, indicating that their role in cancer initiation, growth and metastasis is complex and context-dependent. Here, we performed genome-wide expression analysis comparing fibroblasts in normal, inflammatory and tumour-associated skin. Cancer-associated fibroblasts (CAFs) exhibit a fibrotic gene signature in wound-induced tumours, demonstrating persistent extracellular matrix (ECM) remodelling within these tumours. A top upregulated gene in mouse CAFs encodes for PRSS35, a protease capable of collagen remodelling. In human skin, we observed PRSS35 expression uniquely in the stroma of high-grade squamous cell carcinomas. Ablation of PRSS35 in mouse models of wound- or chemically-induced tumorigenesis resulted in aberrant collagen composition in the ECM and increased tumour incidence. Our results indicate that fibrotic enzymes expressed by CAFs can regulate squamous tumour initiation by remodelling the ECM.
Identifiants
pubmed: 33780134
doi: 10.15252/embr.202051573
pmc: PMC8097359
doi:
Banques de données
GEO
['GSE156197']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e51573Informations de copyright
© 2021 The Authors.
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