Hypoxia induces macrophages to highly express TREM-1 exosome to promote EMT,invasion,and migration of ovarian cancer cells
10.3969/j.issn.1000-484X.2025.10.028
- VernacularTitle:低氧诱导巨噬细胞高表达TREM-1外泌体以促进卵巢癌细胞的EMT、侵袭及迁移
- Author:
Han CHEN
1
;
Jiangyi YANG
;
Hua CHEN
;
Fen HUANG
;
Feng HAN
Author Information
1. 海南医学院第一附属医院检验科,海口 570102
- Publication Type:Journal Article
- Keywords:
Ovarian cancer;
TREM-1;
Macrophages;
Exosomes;
Invasion
- From:
Chinese Journal of Immunology
2025;41(10):2475-2481
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of hypoxemia(HYP)on the expression of myeloid cell trigger receptor-1(TREM-1)in macrophage exosomes(Exo)and the effect of TREM-1 on the biological behavior of ovarian cancer cells.Methods:The expression of TREM-1 in 27 cases of epithelial ovarian cancer tissues and 30 cases of benign ovarian cysts were detected by immuno-histochemical staining.The human mononuclear cell line THP-1 was induced into macrophages by chemical induction method,and the siRNA silencing TREM-1 was transfected into the differentiated macrophages under HYP conditions.The macrophages Exo derived from normoxia(NOR)and HYP were isolated and co-cultured with the ovarian cancer cell line SKOV3.The cells were divided into the NOR-Exo group,HYP-Exo-siRNA group,HYP-Exo-siTREM-1 group and Control group.Transwell assay,scratch assay and Western blot were used to detect the invasion,migration,epithelial-mesenchymal transition(EMT)ability of ovarian cancer cells in each group,the expression of TREM-1 protein in cells,and the protein phosphorylation levels of P65,ERK1/2 and AKT in the NF-κB,ERK1/2 and AKT signaling pathways,respectively.Results:Compared with benign ovarian cyst,the expression of TREM-1 in ovarian cancer macrophage was significantly increased(P<0.05).Compared with NOR,HYP could significantly promote the expression of TREM-1 in macrophage and its Exo(P<0.05).Compared with Control group,the invasion,migration and EMT ability and the protein phosphorylation levels of P65,ERK1/2 and AKT in HYP-Exo-siRNA group and HYP-Exo-siTREM-1 group were significantly in-creased(P<0.05),there was no significant change in the NOR-Exo group(P>0.05).Compared with HYP-Exo-siRNA group,the above detection indexes in NOR-Exo group and HYP-Exo-siTREM-1 group were significantly decreased(P<0.05).Conclusion:HYP can up-regulate the EMT,invasion and migration ability of ovarian cancer cells by promoting the high expression of TREM-1 in Exo de-rived from macrophages,which may be related to the activation of NF-κB,ERK1/2 and AKT signaling pathways.
