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M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells
BACKGROUND AND AIMS: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor‐associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mec...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360085/ https://www.ncbi.nlm.nih.gov/pubmed/32594528 http://dx.doi.org/10.1002/hep.31432 |
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author | Wu, Jindao Gao, Wen Tang, Qiyun Yu, Yue You, Wei Wu, Zhengshan Fan, Ye Zhang, Long Wu, Chen Han, Guoyong Zuo, Xueliang Zhang, Yao Chen, Zhiqiang Ding, Wenzhou Li, Xiangcheng Lin, Fengming Shen, Hongbing Tang, Jinhai Zhang, Yaqin Wang, Xuehao |
author_facet | Wu, Jindao Gao, Wen Tang, Qiyun Yu, Yue You, Wei Wu, Zhengshan Fan, Ye Zhang, Long Wu, Chen Han, Guoyong Zuo, Xueliang Zhang, Yao Chen, Zhiqiang Ding, Wenzhou Li, Xiangcheng Lin, Fengming Shen, Hongbing Tang, Jinhai Zhang, Yaqin Wang, Xuehao |
author_sort | Wu, Jindao |
collection | PubMed |
description | BACKGROUND AND AIMS: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor‐associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro‐metastatic effect of TAMs on HCC remains undefined. APPROACH AND RESULTS: The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2‐polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo. Furthermore, we found that M2‐derived exosomes induced TAM‐mediated pro‐migratory activity. With the use of mass spectrometry, we identified that integrin, α(M)β(2) (CD11b/CD18), was notably specific and efficient in M2 macrophage–derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos–mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase‐9 signaling pathway in recipient HCC cells to support tumor migration. CONCLUSIONS: Collectively, the exosome‐mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis. |
format | Online Article Text |
id | pubmed-8360085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83600852021-08-17 M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells Wu, Jindao Gao, Wen Tang, Qiyun Yu, Yue You, Wei Wu, Zhengshan Fan, Ye Zhang, Long Wu, Chen Han, Guoyong Zuo, Xueliang Zhang, Yao Chen, Zhiqiang Ding, Wenzhou Li, Xiangcheng Lin, Fengming Shen, Hongbing Tang, Jinhai Zhang, Yaqin Wang, Xuehao Hepatology Original Articles BACKGROUND AND AIMS: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor‐associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro‐metastatic effect of TAMs on HCC remains undefined. APPROACH AND RESULTS: The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2‐polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo. Furthermore, we found that M2‐derived exosomes induced TAM‐mediated pro‐migratory activity. With the use of mass spectrometry, we identified that integrin, α(M)β(2) (CD11b/CD18), was notably specific and efficient in M2 macrophage–derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos–mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase‐9 signaling pathway in recipient HCC cells to support tumor migration. CONCLUSIONS: Collectively, the exosome‐mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis. John Wiley and Sons Inc. 2021-04-13 2021-04 /pmc/articles/PMC8360085/ /pubmed/32594528 http://dx.doi.org/10.1002/hep.31432 Text en © 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Wu, Jindao Gao, Wen Tang, Qiyun Yu, Yue You, Wei Wu, Zhengshan Fan, Ye Zhang, Long Wu, Chen Han, Guoyong Zuo, Xueliang Zhang, Yao Chen, Zhiqiang Ding, Wenzhou Li, Xiangcheng Lin, Fengming Shen, Hongbing Tang, Jinhai Zhang, Yaqin Wang, Xuehao M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title | M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title_full | M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title_fullStr | M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title_full_unstemmed | M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title_short | M2 Macrophage–Derived Exosomes Facilitate HCC Metastasis by Transferring α(M)β(2) Integrin to Tumor Cells |
title_sort | m2 macrophage–derived exosomes facilitate hcc metastasis by transferring α(m)β(2) integrin to tumor cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360085/ https://www.ncbi.nlm.nih.gov/pubmed/32594528 http://dx.doi.org/10.1002/hep.31432 |
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