Exosomes derived from gastric cancer cells promote phenotypic transformation of hepatic stellate cells and affect the malignant behavior of gastric cancer cells.
Humans
Stomach Neoplasms
/ pathology
Exosomes
/ metabolism
Hepatic Stellate Cells
/ metabolism
Epithelial-Mesenchymal Transition
Cell Proliferation
Cell Movement
Cell Line, Tumor
beta Catenin
/ metabolism
Cell Transformation, Neoplastic
/ genetics
Gene Expression Regulation, Neoplastic
Actins
/ metabolism
Phenotype
Journal
Journal of cancer research and therapeutics
ISSN: 1998-4138
Titre abrégé: J Cancer Res Ther
Pays: India
ID NLM: 101249598
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
received:
03
04
2023
accepted:
01
03
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
29
8
2024
Statut:
ppublish
Résumé
This study aimed to evaluate the effect of exosomes derived from gastric cancer cells on the phenotypic transformation of hepatic stellate cells (HSCs) and the effect of HSC activation on the malignant behavior of gastric cancer cells, including its molecular mechanism. Exosomes derived from the human gastric adenocarcinoma cell line AGS were extracted and purified by polymer precipitation and ultrafiltration, respectively. The exosomes' morphologic characteristics were observed using transmission electron microscopy, particle size was determined through nanoparticle-tracking analysis, and marker proteins were detected using western blotting. Exosome uptake by LX-2 HSCs was observed through fluorescence-based tracing. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the messenger RNA (mRNA) expression of alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Using functional assays, the effects of LX-2 HSC activation on the biological behavior of malignant gastric cancer cells were evaluated. The effects of LX-2 HSC activation on the protein expression of epithelial-mesenchymal transition (EMT)-related genes and β-catenin were evaluated via western blotting. The extracted particles conformed to the definitions of exosomes and were thus considered gastric cancer cell-derived exosomes. Fluorescence-based tracing successfully demonstrated that exosomes were enriched in LX-2 HSCs. RT-qPCR revealed that the mRNA expression of the cancer-associated fibroblast markers α-SMA and FAP was significantly increased. LX-2 HSC activation considerably enhanced gastric cancer cell proliferation, invasion, and migration. Western blotting showed that the expression of the EMT-related epithelial marker E-cadherin was significantly downregulated, whereas the expression of interstitial markers (N-cadherin and vimentin) and β-catenin was remarkably upregulated in gastric cancer cells. Exosomes derived from gastric cancer cells promoted phenotypic transformation of HSCs and activated HSCs to become tumor-associated fibroblasts. Gastric cancer cell-derived cells significantly enhanced gastric cancer cell proliferation, invasion, and migration after HSC activation, which may promote EMT of gastric cancer cells through the Wnt/β-catenin pathway.
Identifiants
pubmed: 39206977
doi: 10.4103/jcrt.jcrt_749_23
pii: 01363817-202420040-00006
doi:
Substances chimiques
beta Catenin
0
Actins
0
CTNNB1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1157-1164Informations de copyright
Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.
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