Fluid Shear Stress-Induced Exosomes from Liver Cancer Cells Promote Activation of Cancer-Associated Fibroblasts via IGF2-PI3K Axis

Frontiers in Bioscience-Landmark

Jia He¹  Fei Fang¹  Xiaoheng Liu¹  Hongchi Yu¹  Chunhe Zhang¹  Tang Feng¹  Tiantian Li¹  Yang Shen¹ 

[1] Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 610041 Chengdu, Sichuan, China;

关键词: fluid shear stress;    cancer-associated fibroblasts;    exosome;    igf2;    cell-cell communication;   

DOI  :  10.31083/j.fbl2703104

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown