title: Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.
abstract: Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Yaoxiang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
authors.forename: Zhaoji
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China. lstmmmlst@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China. icls@ujs.edu.cn.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D055354:Exosomes / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D016328:NF-kappa B
keywords: Exosomes; Gastric cancer; Macrophages; Microenvironment; NF-κB