Meningioma Tumor Microenvironment

Negah, Sajad Sahab; Gorji, Ali

doi:10.1007/978-3-030-59038-3_3

Cited by 6 publications

(2 citation statements)

References 108 publications

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“…Despite improvements in the treatment of meningiomas over the past decade, the role of the TME in meningioma development remains unclear. Previous studies have suggested that a variety of stromal cells, including TAMs, interact with tumor cells in the TME, which contributes to tumor progression [ 14 , 15 , 17 ]. However, the molecular mechanisms underlying the integral role of infiltrating TAMs in the development of malignant meningiomas have not been fully studied.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Journal of Immunology Research

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Journal of Immunology Research

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“…Some meningioma variants have also been shown to be associated with systemic inflammatory syndromes ( Polyzoidis et al, 2015 ). Other studies have shown that the proportion of immune cells changes significantly during the development of meningiomas, suggesting that meningiomas also affect the immune response process ( Sahab-Negah and Gorji, 2020 ). However, reverse causality and residual confounding are common biases in these traditional observational studies.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study

et al. 2023

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BackgroundMeningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear.MethodMendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It’s a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome.ResultsThis research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-β, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood.ConclusionThese findings suggest that TNF-β, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas.

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Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

Huang

et al. 2023

Advanced Science

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High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1 + ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1 + and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1 + in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

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Meningioma Tumor Microenvironment

Cited by 6 publications

References 108 publications

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

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

Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

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