ArticleOncotarget2016
Hypoxia promotes glioma-associated macrophage infiltration via periostin and subsequent M2 polarization by upregulating TGF-beta and M-CSFR.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 162 citations in OpenAlex.
- FAPExperimental & molecular medicine · 2026Article
- LAMP2 drives M2 macrophage polarization and promotes glioma progression through autophagy.Discover oncology · 2026Article
- Review
- Review
- Crossroads of cell fate: miR-34-mediated regulation of apoptosis and autophagy in glioblastoma.Discover oncology · 2025Review
- Research progress on macrophages in cardiovascular diseases.Journal of cardiothoracic surgery · 2025Review
- Glioblastoma- derived exosomes (GBM-Exo) regulate microglial M2 polarization via the RAC1/AKT/NRF2 pathway.Journal of neuro-oncology · 2025Article
- Emerging macrophage-based therapies for cancer: a review of preclinical and clinical advances.Frontiers in immunology · 2025Review
- Silencing epileptic storms: targeting miRNA-lncRNA crosstalk in astrocytes and microglia to disarm neuroinflammatory triggers.Frontiers in molecular neuroscience · 2025Review
- Review
- Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.Translational psychiatry · 2024Article
- Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy.Clinical and experimental medicine · 2024Review
- Tumor-derived extracellular vesicle proteins as new biomarkers and targets in precision oncology.Journal of molecular medicine (Berlin, Germany) · 2024Review
- An Update on the Clinical Status, Challenges, and Future Directions of Oncolytic Virotherapy for Malignant Gliomas.Current treatment options in oncology · 2024Review
- Effect of hypoxia‑HIF‑1α‑periostin axis in thyroid cancer.Oncology reports · 2024Article
- Exploring personalized treatment for cardiac graft rejection based on a four-archetype analysis model and bioinformatics analysis.Scientific reports · 2024Article
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- Current progression in application of extracellular vesicles in central nervous system diseases.European journal of medical research · 2024Review
- Neuroinflammation in Glioblastoma: The Role of the Microenvironment in Tumour Progression.Current cancer drug targets · 2024Review
- Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.Frontiers in immunology · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) are enriched in gliomas and help create a tumor-immunosuppressive microenvironment. A distinct M2-skewed type of macrophages makes up the majority of glioma TAMs, and these cells exhibit pro-tumor functions. Gliomas contain large hypoxic areas, and the presence of a correlation between the density of M2-polarized TAMs and hypoxic areas suggests that hypoxia plays a supportive role during TAM recruitment and induction. Here, we investigated the effects of hypoxia on human macrophage recruitment and M2 polarization. We also investigated the influence of the HIF inhibitor acriflavine (ACF) on M2 TAM infiltration and tumor progression in vivo. We found that hypoxia increased periostin (POSTN) expression in glioma cells and promoted the recruitment of macrophages. Hypoxia-inducible POSTN expression was increased by TGF-α via the RTK/PI3K pathway, and this effect was blocked by treating hypoxic cells with ACF. We also demonstrated that both a hypoxic environment and hypoxia-treated glioma cell supernatants were capable of polarizing macrophages toward a M2 phenotype. ACF partially reversed the M2 polarization of macrophages by inhibiting the upregulation of M-CSFR in macrophages and TGF-β in glioma cells under hypoxic conditions. Administering ACF also ablated tumor progression in vivo. Our findings reveal a mechanism that underlies hypoxia-induced TAM enrichment and M2 polarization and suggest that pharmacologically inhibiting HIFs may reduce M2-polarized TAM infiltration and glioma progression.
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Registered trials
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 OpenQuestion graph.