ArticleJournal of neuroinflammation2022
Complement C3a activates astrocytes to promote medulloblastoma progression through TNF-α.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.International journal of molecular sciences · 2026Review
- Therapeutic effect and anti-inflammatory mechanism of modified Shoutai pills against lipopolysaccharide-induced miscarriage in mice.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- M28 family peptidase derived fromGut microbes · 2025Article
- Review
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Therapeutic approaches for targeting the pediatric brain tumor microenvironment.Drug delivery and translational research · 2025Review
- METTL1-mediated mCell death & disease · 2025Article
- Multi-omics analysis reveals key immunogenic signatures induced by oncolytic Zika virus infection of paediatric brain tumour cells.Scientific reports · 2025Article
- Construction of an Extracellular Matrix-Related Risk Model to Analyze the Correlation Between Glioblastoma and Tumor Immunity.BioMed research international · 2025Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- The complement C3a/C3aR pathway is associated with treatment resistance to gemcitabine-based neoadjuvant therapy in pancreatic cancer.Computational and structural biotechnology journal · 2024Article
- Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity with High-Density Progenitor Cell Regions Correlating with High-Risk Disease.bioRxiv : the preprint server for biology · 2024Article
- Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2.Brain pathology (Zurich, Switzerland) · 2024Article
- A novel CD47-blocking peptide fused to pro-apoptotic KLA repeat inhibits lung cancer growth in mice.Cancer immunology, immunotherapy : CII · 2023Article
- Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts.International journal of molecular sciences · 2023Article
- Identification of efferocytosis-related subtypes in gliomas and elucidating their characteristics and clinical significance.Frontiers in cell and developmental biology · 2023Article
- Comparative proteomics of human milk casein fraction collected from women of Korean and Han ethnic groups in China.Frontiers in nutrition · 2023Article
- The Tumor Microenvironment of Medulloblastoma: An Intricate Multicellular Network with Therapeutic Potential.Cancers · 2022Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMedulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one-third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is, therefore, critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute the tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms by which astrocytes are regulated and activated to promote MB remain elusive.
methodsBy taking advantage of Math1-Cre/Ptch1
resultsWe found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via the p38 MAPK pathway. Moreover, we discovered that C3a upregulated the production of proinflammatory cytokines, such as IL-6 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with a TNF-α receptor antagonist, indicating a TNF-α-dependent event. Indeed, we further demonstrated that administration of a selective C3a receptor or TNF-α receptor antagonist to mice subcutaneously transplanted with MB suppressed tumor progression in vivo.
conclusionsC3a was released during MB development. C3a triggered astrocyte activation and TNF-α production via the p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. These findings imply that targeting C3a and TNF-α may represent a potential novel therapeutic approach for human MB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.