Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization
The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation...
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4122 |
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| author | Jing Song Peiyan Yang Xiuwen Li Xinyi Zhu Mengxin Liu Xuexin Duan Ran Liu |
| author_facet | Jing Song Peiyan Yang Xiuwen Li Xinyi Zhu Mengxin Liu Xuexin Duan Ran Liu |
| author_sort | Jing Song |
| collection | DOAJ |
| description | The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs. |
| first_indexed | 2024-03-10T08:56:45Z |
| format | Article |
| id | doaj.art-ab9f8dc627dd4bda8e8e7e4693bb3f4e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:56:45Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ab9f8dc627dd4bda8e8e7e4693bb3f4e2023-11-22T07:04:07ZengMDPI AGCancers2072-66942021-08-011316412210.3390/cancers13164122Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage PolarizationJing Song0Peiyan Yang1Xiuwen Li2Xinyi Zhu3Mengxin Liu4Xuexin Duan5Ran Liu6Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaThe Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaThe Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaState Key Laboratory of Precision Measuring Technology & Instruments, College of Precision Instrument and Opto-electronics Engineering, Tianjin University, Tianjin 300072, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaThe disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs.https://www.mdpi.com/2072-6694/13/16/4122esophageal squamous cell carcinoma (ESCC)EVs-miR-21-5pmacrophage polarizationepithelial-mesenchymal transition |
| spellingShingle | Jing Song Peiyan Yang Xiuwen Li Xinyi Zhu Mengxin Liu Xuexin Duan Ran Liu Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization Cancers esophageal squamous cell carcinoma (ESCC) EVs-miR-21-5p macrophage polarization epithelial-mesenchymal transition |
| title | Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization |
| title_full | Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization |
| title_fullStr | Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization |
| title_full_unstemmed | Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization |
| title_short | Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization |
| title_sort | esophageal cancer derived extracellular vesicle mir 21 5p contributes to emt of escc cells by disorganizing macrophage polarization |
| topic | esophageal squamous cell carcinoma (ESCC) EVs-miR-21-5p macrophage polarization epithelial-mesenchymal transition |
| url | https://www.mdpi.com/2072-6694/13/16/4122 |
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