M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway

Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study,...

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Main Authors: Xiao-Hong Fu, Jian-Ping Li, Xue-Ying Li, Yan Tan, Min Zhao, Shao-Fu Zhang, Xue-Dong Wu, Jian-Guo Xu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/8326591
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author Xiao-Hong Fu
Jian-Ping Li
Xue-Ying Li
Yan Tan
Min Zhao
Shao-Fu Zhang
Xue-Dong Wu
Jian-Guo Xu
author_facet Xiao-Hong Fu
Jian-Ping Li
Xue-Ying Li
Yan Tan
Min Zhao
Shao-Fu Zhang
Xue-Dong Wu
Jian-Guo Xu
author_sort Xiao-Hong Fu
collection DOAJ
description Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression. Methods. First, the distribution and functional phenotype of macrophages in meningioma tissues were assessed by immunohistochemistry. Macrophage-derived exosomes (MDEs) were characterized, and further cell coculture experiments were performed to explore the effects of M2-MDEs on the proliferation, migration, and invasion of meningioma cells. RNA sequencing was used to analyze the transcriptomic signatures in meningioma cells treated with M2-MDEs. Three-dimensional tumorspheres and xenograft tumor models were used to evaluate the effects of M2-MDEs on meningioma tumorigenesis and development. Results. We found that M2 macrophages were enriched in meningioma tissue. Coculture with meningioma cells induced the M2 polarization of macrophages. We also found that M2-MDEs were able to significantly promote cell proliferation, cell migration, cell invasion, and tumorigenesis in meningiomas. Bioinformatic analysis suggested that the TGF-β pathway was activated in meningioma cells treated with M2-MDEs. Functional experiments demonstrated that blocking the TGF-β signaling pathway could effectively reverse the tumor-promotive effects mediated by M2-MDEs. Conclusions. Overall, our study showed that M2-MDEs promoted meningioma development and invasion by activating the TGF-β signaling pathway. Targeting exosome-mediated intercellular communication in the tumor microenvironment may be a novel therapeutic strategy for meningioma patients.
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spelling doaj-art-bd4616981c3a4a92b38fd70f352da3452025-08-20T03:23:19ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/8326591M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling PathwayXiao-Hong Fu0Jian-Ping Li1Xue-Ying Li2Yan Tan3Min Zhao4Shao-Fu Zhang5Xue-Dong Wu6Jian-Guo Xu7Department of NeurosurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of OphthalmologyDepartment of PharmacyDepartment of NeurosurgeryDepartment of NeurosurgeryDepartment of NeurosurgeryTumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression. Methods. First, the distribution and functional phenotype of macrophages in meningioma tissues were assessed by immunohistochemistry. Macrophage-derived exosomes (MDEs) were characterized, and further cell coculture experiments were performed to explore the effects of M2-MDEs on the proliferation, migration, and invasion of meningioma cells. RNA sequencing was used to analyze the transcriptomic signatures in meningioma cells treated with M2-MDEs. Three-dimensional tumorspheres and xenograft tumor models were used to evaluate the effects of M2-MDEs on meningioma tumorigenesis and development. Results. We found that M2 macrophages were enriched in meningioma tissue. Coculture with meningioma cells induced the M2 polarization of macrophages. We also found that M2-MDEs were able to significantly promote cell proliferation, cell migration, cell invasion, and tumorigenesis in meningiomas. Bioinformatic analysis suggested that the TGF-β pathway was activated in meningioma cells treated with M2-MDEs. Functional experiments demonstrated that blocking the TGF-β signaling pathway could effectively reverse the tumor-promotive effects mediated by M2-MDEs. Conclusions. Overall, our study showed that M2-MDEs promoted meningioma development and invasion by activating the TGF-β signaling pathway. Targeting exosome-mediated intercellular communication in the tumor microenvironment may be a novel therapeutic strategy for meningioma patients.http://dx.doi.org/10.1155/2022/8326591
spellingShingle Xiao-Hong Fu
Jian-Ping Li
Xue-Ying Li
Yan Tan
Min Zhao
Shao-Fu Zhang
Xue-Dong Wu
Jian-Guo Xu
M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
Journal of Immunology Research
title M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
title_full M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
title_fullStr M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
title_full_unstemmed M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
title_short M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway
title_sort m2 macrophage derived exosomes promote meningioma progression through tgf β signaling pathway
url http://dx.doi.org/10.1155/2022/8326591
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