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.
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This work was supported by the National Natural Science Foundation of China (81572075, 81201660), the Natural Science Foundation of the Jiangsu Province (BK20141303), Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities (SJK2013-10), Jiangsu Province’s Outstanding Medical Academic Leader and Sci-tech Innovation Team Program (LJ201117), Jiangsu Province’s Major Project in Research and Development (BE2015667), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
The medical ethics committee of Jiangsu University approved this study.
Conflicts of interest
Lijun Wu and Xu Zhang contributed equally to this work.
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Wu, L., Zhang, X., Zhang, B. et al. Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression. Tumor Biol. 37, 12169–12180 (2016). https://doi.org/10.1007/s13277-016-5071-5
- Gastric cancer