Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes
Epithelial-mesenchymal transition (EMT) is a major event during cancer progression and metastasis; however, the definitive role of EMT in remodeling tumor microenvironments (TMEs) is unclear. Tumor-associated macrophages (TAMs) are a major type of host immune cells in TMEs, and they perform a wide r...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618301209 |
| _version_ | 1818310902042066944 |
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| author | Chia-Hsin Hsieh Shyh-Kuan Tai Muh-Hwa Yang |
| author_facet | Chia-Hsin Hsieh Shyh-Kuan Tai Muh-Hwa Yang |
| author_sort | Chia-Hsin Hsieh |
| collection | DOAJ |
| description | Epithelial-mesenchymal transition (EMT) is a major event during cancer progression and metastasis; however, the definitive role of EMT in remodeling tumor microenvironments (TMEs) is unclear. Tumor-associated macrophages (TAMs) are a major type of host immune cells in TMEs, and they perform a wide range of functions to regulate tumor colonization and progression by regulating tumor invasiveness, local tumor immunity, and angiogenesis. TAMs are considered to have an M2-like, i.e., alternatively activated, phenotype; however, how these EMT-undergoing cancer cells promote M2 polarization of TAMs as a crucial tumor-host interplay during cancer progression is unclear. In this study, we investigated the mechanism of EMT-mediated TAM activation. Here, we demonstrate that the EMT transcriptional factor Snail directly activates the transcription of MIR21 to produce miR-21-abundant tumor-derived exosomes (TEXs). The miR-21-containing exosomes were engulfed by CD14+ human monocytes, suppressing the expression of M1 markers and increasing that of M2 markers. Knockdown of miR-21 in Snail-expressing human head and neck cancer cells attenuated the Snail-induced M2 polarization, angiogenesis, and tumor growth. In head and neck cancer samples, a high expression of miR-21 was correlated with a higher level of SNAI1 and the M2 marker MRC1. This study elucidates the mechanism of EMT-mediated M2 polarization through delivery of the miR-21-abundant exosomes, which may serve as a candidate biomarker of tumor progression and provide a potential target for intercepting EMT-mediated TME remodeling. |
| first_indexed | 2024-12-13T07:53:26Z |
| format | Article |
| id | doaj.art-c87c16db56a94f5983c363853aed7f14 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-13T07:53:26Z |
| publishDate | 2018-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-c87c16db56a94f5983c363853aed7f142022-12-21T23:54:37ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862018-08-01208775788Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant ExosomesChia-Hsin Hsieh0Shyh-Kuan Tai1Muh-Hwa Yang2Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, TaiwanDepartment of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan; Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, Taiwan; Cancer Progression Research Center, National Yang-Ming University, Taipei 11221, Taiwan; Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan; Address all correspondence to: Muh-Hwa Yang, Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Taipei 11221, Taiwan.Epithelial-mesenchymal transition (EMT) is a major event during cancer progression and metastasis; however, the definitive role of EMT in remodeling tumor microenvironments (TMEs) is unclear. Tumor-associated macrophages (TAMs) are a major type of host immune cells in TMEs, and they perform a wide range of functions to regulate tumor colonization and progression by regulating tumor invasiveness, local tumor immunity, and angiogenesis. TAMs are considered to have an M2-like, i.e., alternatively activated, phenotype; however, how these EMT-undergoing cancer cells promote M2 polarization of TAMs as a crucial tumor-host interplay during cancer progression is unclear. In this study, we investigated the mechanism of EMT-mediated TAM activation. Here, we demonstrate that the EMT transcriptional factor Snail directly activates the transcription of MIR21 to produce miR-21-abundant tumor-derived exosomes (TEXs). The miR-21-containing exosomes were engulfed by CD14+ human monocytes, suppressing the expression of M1 markers and increasing that of M2 markers. Knockdown of miR-21 in Snail-expressing human head and neck cancer cells attenuated the Snail-induced M2 polarization, angiogenesis, and tumor growth. In head and neck cancer samples, a high expression of miR-21 was correlated with a higher level of SNAI1 and the M2 marker MRC1. This study elucidates the mechanism of EMT-mediated M2 polarization through delivery of the miR-21-abundant exosomes, which may serve as a candidate biomarker of tumor progression and provide a potential target for intercepting EMT-mediated TME remodeling.http://www.sciencedirect.com/science/article/pii/S1476558618301209 |
| spellingShingle | Chia-Hsin Hsieh Shyh-Kuan Tai Muh-Hwa Yang Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes Neoplasia: An International Journal for Oncology Research |
| title | Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes |
| title_full | Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes |
| title_fullStr | Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes |
| title_full_unstemmed | Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes |
| title_short | Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes |
| title_sort | snail overexpressing cancer cells promote m2 like polarization of tumor associated macrophages by delivering mir 21 abundant exosomes |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618301209 |
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