Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5.
Antineoplastic Agents
/ pharmacology
Cancer-Associated Fibroblasts
/ drug effects
Carcinoma, Pancreatic Ductal
/ genetics
Cell Proliferation
/ drug effects
Collagen
/ genetics
Ephrin-A5
/ genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Neoadjuvant Therapy
Pancreatic Neoplasms
/ genetics
Primary Cell Culture
Retrospective Studies
Signal Transduction
Tumor Cells, Cultured
Tumor Microenvironment
/ drug effects
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
28
09
2020
accepted:
10
11
2021
revised:
26
10
2021
pubmed:
27
11
2021
medline:
11
3
2022
entrez:
26
11
2021
Statut:
ppublish
Résumé
The treatment of pancreatic cancer (PDAC) remains clinically challenging, and neoadjuvant therapy (NAT) offers down staging and improved surgical resectability. Abundant fibrous stroma is involved in malignant characteristic of PDAC. We aimed to investigate tissue remodelling, particularly the alteration of the collagen architecture of the PDAC microenvironment by NAT. We analysed the alteration of collagen and gene expression profiles in PDAC tissues after NAT. Additionally, we examined the biological role of Ephrin-A5 using primary cultured cancer-associated fibroblasts (CAFs). The expression of type I, III, IV, and V collagen was reduced in PDAC tissues after effective NAT. The bioinformatics approach provided comprehensive insights into NAT-induced matrix remodelling, which showed Ephrin-A signalling as a likely pathway and Ephrin-A5 (encoded by EFNA5) as a crucial ligand. Effective NAT reduced the number of Ephrin-A5 These results suggest that effective NAT changes the extracellular matrix with collagen profiles through CAFs and their Ephrin-A5 expression.
Sections du résumé
BACKGROUND
The treatment of pancreatic cancer (PDAC) remains clinically challenging, and neoadjuvant therapy (NAT) offers down staging and improved surgical resectability. Abundant fibrous stroma is involved in malignant characteristic of PDAC. We aimed to investigate tissue remodelling, particularly the alteration of the collagen architecture of the PDAC microenvironment by NAT.
METHODS
We analysed the alteration of collagen and gene expression profiles in PDAC tissues after NAT. Additionally, we examined the biological role of Ephrin-A5 using primary cultured cancer-associated fibroblasts (CAFs).
RESULTS
The expression of type I, III, IV, and V collagen was reduced in PDAC tissues after effective NAT. The bioinformatics approach provided comprehensive insights into NAT-induced matrix remodelling, which showed Ephrin-A signalling as a likely pathway and Ephrin-A5 (encoded by EFNA5) as a crucial ligand. Effective NAT reduced the number of Ephrin-A5
CONCLUSION
These results suggest that effective NAT changes the extracellular matrix with collagen profiles through CAFs and their Ephrin-A5 expression.
Identifiants
pubmed: 34824448
doi: 10.1038/s41416-021-01639-9
pii: 10.1038/s41416-021-01639-9
pmc: PMC8854423
doi:
Substances chimiques
Antineoplastic Agents
0
Ephrin-A5
0
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
628-639Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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