Fluid Shear Stress-Induced Exosomes from Liver Cancer Cells Promote Activation of Cancer-Associated Fibroblasts via IGF2-PI3K Axis.
IGF2
cancer-associated fibroblasts
cell-cell communication
exosome
fluid shear stress
Journal
Frontiers in bioscience (Landmark edition)
ISSN: 2768-6698
Titre abrégé: Front Biosci (Landmark Ed)
Pays: Singapore
ID NLM: 101612996
Informations de publication
Date de publication:
17 03 2022
17 03 2022
Historique:
received:
15
01
2022
revised:
20
02
2022
accepted:
02
03
2022
entrez:
29
3
2022
pubmed:
30
3
2022
medline:
23
4
2022
Statut:
ppublish
Résumé
Cancer-associated fibroblasts (CAFs) are of considerable importance in tumor progression by interacting with the tumor microenvironment. However, the hidden mechanism explaining how tumor cells interact with CAFs in the tumor mechanical microenvironment remains largely unknown. We highlighted exosomes as the mediator modulating the interaction between liver cancer cells and CAFs under mechanical conditions. The normal hepatic stellate cells LX2 were exposed to the medium or exosomes from the HepG2 cells with or without fluid shear stress subjection, and the CAFs activation markers were checked. To further explore the potential role of PI3K, which is active in liver fibrosis, the PI3K inhibitor was used. The specific markers of CAFs, FAP, and α-SMA, increased in LX2 with subjection to the fluid shear stress-induced exosomes from HepG2 cells. In turn, the enriched IGF2 in the exosomes activated the IGF2-PI3K signaling pathway in LX2 cells. These findings reveal that fluid shear stress-induced liver cancer cells possess a stronger capacity to convert normal fibroblasts to CAFs than statically cultured liver cancer cells, and tumor-derived exosomes mediated the intercellular cross-talk between liver cancer cells and fibroblasts.
Sections du résumé
BACKGROUND
Cancer-associated fibroblasts (CAFs) are of considerable importance in tumor progression by interacting with the tumor microenvironment. However, the hidden mechanism explaining how tumor cells interact with CAFs in the tumor mechanical microenvironment remains largely unknown.
METHODS
We highlighted exosomes as the mediator modulating the interaction between liver cancer cells and CAFs under mechanical conditions. The normal hepatic stellate cells LX2 were exposed to the medium or exosomes from the HepG2 cells with or without fluid shear stress subjection, and the CAFs activation markers were checked. To further explore the potential role of PI3K, which is active in liver fibrosis, the PI3K inhibitor was used.
RESULTS
The specific markers of CAFs, FAP, and α-SMA, increased in LX2 with subjection to the fluid shear stress-induced exosomes from HepG2 cells. In turn, the enriched IGF2 in the exosomes activated the IGF2-PI3K signaling pathway in LX2 cells.
CONCLUSIONS
These findings reveal that fluid shear stress-induced liver cancer cells possess a stronger capacity to convert normal fibroblasts to CAFs than statically cultured liver cancer cells, and tumor-derived exosomes mediated the intercellular cross-talk between liver cancer cells and fibroblasts.
Identifiants
pubmed: 35345336
pii: S2768-6701(22)00442-7
doi: 10.31083/j.fbl2703104
doi:
Substances chimiques
IGF2 protein, human
0
Insulin-Like Growth Factor II
67763-97-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Informations de copyright
© 2022 The Author(s). Published by IMR Press.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.