M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma
Abstract Background Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-022-00872-w |
| _version_ | 1797636738933325824 |
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| author | Yiwei Lu Guoyong Han Yao Zhang Long Zhang Zhi Li Qingyuan Wang Zhiqiang Chen Xuehao Wang Jindao Wu |
| author_facet | Yiwei Lu Guoyong Han Yao Zhang Long Zhang Zhi Li Qingyuan Wang Zhiqiang Chen Xuehao Wang Jindao Wu |
| author_sort | Yiwei Lu |
| collection | DOAJ |
| description | Abstract Background Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation. Methods THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed. Results M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages. Conclusions Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstract |
| first_indexed | 2024-03-11T12:39:24Z |
| format | Article |
| id | doaj.art-281196f5ab4f431bbff7b5a80e087eff |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-11T12:39:24Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-281196f5ab4f431bbff7b5a80e087eff2023-11-05T12:25:04ZengBMCCell Communication and Signaling1478-811X2023-10-0121111610.1186/s12964-022-00872-wM2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinomaYiwei Lu0Guoyong Han1Yao Zhang2Long Zhang3Zhi Li4Qingyuan Wang5Zhiqiang Chen6Xuehao Wang7Jindao Wu8Department of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation. Methods THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed. Results M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages. Conclusions Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstracthttps://doi.org/10.1186/s12964-022-00872-wM2 macrophagesExosomesEMTAngiogenesisVascular permeabilitymiR-23a-3p |
| spellingShingle | Yiwei Lu Guoyong Han Yao Zhang Long Zhang Zhi Li Qingyuan Wang Zhiqiang Chen Xuehao Wang Jindao Wu M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma Cell Communication and Signaling M2 macrophages Exosomes EMT Angiogenesis Vascular permeability miR-23a-3p |
| title | M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| title_full | M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| title_fullStr | M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| title_full_unstemmed | M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| title_short | M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| title_sort | m2 macrophage secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma |
| topic | M2 macrophages Exosomes EMT Angiogenesis Vascular permeability miR-23a-3p |
| url | https://doi.org/10.1186/s12964-022-00872-w |
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