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

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.

Proteome of human glioblastoma and meningioma tissue small extracellular vesicles

“…When these were compared against the MNG EV proteins we identified, a total of 11 common proteins were identified (PGK1, ALDOA, ANAXA1, HSPB1, PFN1, PKM, S100A11, SPTBN1, SPTAN1, PLEC and TF). Our study not only confirms the presence of proteins previously identified in MNG EVs (4,(7)(8)(9)(10)(11)(12)25), but also identified novel proteins that have not been previously reported in association with MNG EVs.…”

“…Differential expression analysis was utilized to reveal the relative abundance of proteins that were enriched in the EVs compared to the tumour tissue. Our study not only confirms the presence of proteins previously identified in GBM EVs from various sources (including CUSA washings, cell lines, and plasma) (4,(7)(8)(9)(10)(11)(12)25), but also crucially identified novel proteins that have not been reported before in association with GBM EVs before including proteins associated with solute carrier transporters and fatty acid transport. Recently it has been shown that solute carrier family members can promote the progression of GBM by activating the PI3-AKT signalling pathway (44).…”

“…Despite progress in understanding the significance of EVs in brain function and the genesis and progression of brain tumours, there is a gap in our knowledge. The majority of prior investigations have primarily been on EVs obtained from patient fluids or cell cultures (4,(7)(8)(9)(10)(11)(12), rather than directly from the tumour tissue itself, which is important as these EVs may not adequately represent the complexity and specificity of those in tumour tissue. Relative to the routine isolation of EVs from fluids, including conditioned cell culture media, blood, urine or CSF, many technical issues must be addressed when isolating EVs directly from solid tissue.…”

Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors

“…According to recent studies, circulating miRNAs such as miRNA 497 and 219 inside the exosomes have the potential to be used as cancer biomarkers in various tumors including meningiomas [ 194 ]. In another study, M2 macrophage-derived exosomes were found to stimulate meningioma progression through the TGF-β signaling pathway [ 195 ]. Fibulin-2 was observed as another marker for differentiating grade II and grade I meningiomas [ 196 ].…”

EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer

“…Macrophages are one of the most prevalent types of immune cells in the TME [ 6 ]. They have two distinct functional subtypes: M1, which inhibits tumor growth by producing pro-inflammatory cytokines [ 7 , 8 ], and M2, which promotes tumor growth by producing anti-inflammatory cytokines [ 9 , 10 ]. The majority of tumor-associated macrophages (TAMs) have characteristics of M2-polarized cells [ 11 , 12 ].…”