Exosomal FZD10 derived from non-small cell lung cancer cells promotes angiogenesis of human umbilical venous endothelial cells in vitro.
10.12122/j.issn.1673-4254.2022.09.11
- Author:
Xiao Feng WU
1
;
Ri Ming ZHAN
1
;
Da Zhao CHENG
1
;
Li CHEN
1
;
Tian Yu WANG
1
;
Xu Dong TANG
1
Author Information
1. Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, China.
- Publication Type:Journal Article
- Keywords:
FZD10;
angiogenesis;
exosomes;
non-small cell lung cancer
- MeSH:
Carcinoma, Non-Small-Cell Lung/metabolism*;
Cell Proliferation;
Culture Media, Conditioned;
Exosomes;
Frizzled Receptors/metabolism*;
Human Umbilical Vein Endothelial Cells/metabolism*;
Humans;
Lung Neoplasms/metabolism*;
MicroRNAs/genetics*;
Neovascularization, Pathologic/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
RNA, Messenger/metabolism*;
RNA, Small Interfering/metabolism*
- From:
Journal of Southern Medical University
2022;42(9):1351-1358
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of exosomal FZD10 derived from non-small cell lung cancer (NSCLC) cells on angiogenesis of human umbilical venous endothelial cells (HUVECs) and explore the possible mechanism.
METHODS:We analyzed the expression of FZD10 in two NSCLC cell lines (95D and H1299 cells), normal human bronchial epithelial cells (BEAS-2B cells) and their exosomes isolated by ultracentrifugation. Cultured HUVECs were treated with the exosomes derived from NSCLC cells or NSCLC cells transfected with FZD10-siRNA, and the changes in tube formation ability of the cells were analyzed using an in vitro angiogenesis assay. ELISA was performed to determine the concentration of VEGFA and Ang-1 in the conditioned media of HUVECs, and RT-qPCR was used to analyze the mRNA levels of VEGFA and Ang-1 in the HUVECs. The effects of exosomal FZD10 on the activation of PI3K, Erk1/2 and YAP/TAZ signaling pathways were evaluated using Western blotting.
RESULTS:Compared with BEAS-2B cells and their exosomes, 95D and H1299 cells and their exosomes all expressed high levels of FZD10 (P < 0.01). The exosomes derived from 95D and H1299 cells significantly enhanced tube formation ability and increased the expressions of VEGFA and Ang-1 protein and mRNA in HUVECs (P < 0.01), but FZD10 knockdown in 95D and H1299 cells obviously inhibited these effects of the exosomes. Exosomal FZD10 knockdown suppressed the activation of PI3K and Erk1/2 signaling pathways, but had no obvious effect on the activation of YAP/TAZ signaling pathway.
CONCLUSION:Exosomal FZD10 derived from NSCLC cells promotes HUVEC angiogenesis in vitro, the mechanism of which may involve the activation of PI3K and Erk1/2 signaling pathways.
