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Exosomal HMGB3 released by glioma cells confers the activation of NLRP3 inflammasome and pyroptosis in tumor-associated macrophages.
- Source :
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Tissue & cell [Tissue Cell] 2024 Jun; Vol. 88, pp. 102406. Date of Electronic Publication: 2024 May 12. - Publication Year :
- 2024
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Abstract
- Background: Previous evidences has highlighted the pivotal role of NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated inflammasomes and pyroptosis activation in driving tumor malignancy and shaping the tumor microenvironment. Herein, we aimed to elucidate the impact of high-mobility group box 3 (HMGB3) released in glioma-derived exosomes on macrophage infiltration in gliomas, NLRP3 inflammasome activation and polarization.<br />Methods: Transcripts and protein levels of HMGB3, and cytokines associated with macrophage phenotypes and pyroptosis were assessed in glioma tissues and cell lines (U251, LN229, T98G, A172) using qRT-PCR and/or Western blot analysis. Exosomes secreted from LN229 and NHA cells were isolated via differential ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and analysis of exosome-related markers. PKH67 staining was employed to examine exosomes uptake by THP-1 differentiated macrophages. Flow cytometry was utilized to assess macrophage pyroptotic rates and polarization-related markers.<br />Results: HMGB3 expression was elevated in glioma tissues, serum samples and tumor cell lines. Kaplan-Meier curves revealed a positive correlation between higher HMGB3 expression and poor overall survival and recurrence-free survival. Moreover, glioma tissues with increased HMGB3 expression exhibited significant upregulation of M2 macrophages markers (CD68, CD206, Arg1) and NLRP3 inflammasome components (NLRP3, IL-1β, ASC), suggesting that HMGB3 was closely associated with macrophage infiltration and NLRP3 inflammasome activation. Notably, HMGB3 was found to be enriched in glioma cell- secreted exosomes and could be internalized by macrophages. Knockdown of HMGB3 in glioma cell exosomes could restrain M2 macrophage polarization, NLRP3 inflammasome activation and pyroptosis.<br />Conclusion: These findings suggested that glioma cells secreted exosomal HMGB3 could facilitate macrophage M2 polarization, pyroptosis and inflammatory infiltration, indicating HMGB3 might be a poor prognosis factor for glioma.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Humans
Cell Line, Tumor
Male
Female
Tumor Microenvironment
Macrophages metabolism
Macrophages pathology
Brain Neoplasms pathology
Brain Neoplasms metabolism
Brain Neoplasms genetics
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Exosomes metabolism
Pyroptosis
Glioma pathology
Glioma metabolism
Glioma genetics
Inflammasomes metabolism
HMGB3 Protein metabolism
HMGB3 Protein genetics
Tumor-Associated Macrophages metabolism
Tumor-Associated Macrophages pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-3072
- Volume :
- 88
- Database :
- MEDLINE
- Journal :
- Tissue & cell
- Publication Type :
- Academic Journal
- Accession number :
- 38761792
- Full Text :
- https://doi.org/10.1016/j.tice.2024.102406