M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway. (20th May 2022)

• Record Type: Journal Article
• Authors: Fu, Xiao-Hong; Li, Jian-Ping; Li, Xue-Ying; Tan, Yan; Zhao, Min; Zhang, Shao-Fu; Wu, Xue-Dong; Xu, Jian-Guo
• Other Names: Wang Fu Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2022(2022)
• Publication Date: 2022-05-20
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2022/8326591
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : 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.