ArticleActa neuropathologica2016
Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 2 of them syntheses that pooled it.
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Who cites it
139 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives.International journal of molecular sciences · 2022Pooled it
- Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma.Acta neuropathologica communications · 2019Pooled it
- Microglia-specificity of different markers is overridden in glioblastoma specimens.Scientific reports · 2026Article
- Spatiotemporal and metabolic heterogeneity of tumor-associated macrophages in glioblastoma: from single-cell insights to therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Bridging MBD3 functions in developmental biology and glioma heterogeneity to immune remodeling with future perspectives.Frontiers in immunology · 2026Review
- Glioblastoma insights: Focus on crosstalk with the suppressive tumor microenvironment and advanced therapeutic strategies.Medicine · 2025Review
- Exploring the Role of Peripheral Macrophages in Glioma Progression: The Metabolic Significance of Cyclooxygenase-2 (COX-2).International journal of molecular sciences · 2025Article
- Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025Review
- The role of microglia in the development of diabetic retinopathy and its potential clinical application.Human cell · 2025Review
- Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli.Immunology · 2025Review
- Review
- Breaking Down Glioma-Microenvironment Crosstalk.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.Biomedicines · 2025Review
- Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery.Current oncology (Toronto, Ont.) · 2024Review
- Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases.Journal of neuroinflammation · 2024Review
- Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach.Journal of neuro-oncology · 2024Article
- Microglia in retinal angiogenesis and diabetic retinopathy.Angiogenesis · 2024Review
- Review
- Review
79 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myeloid cells are an essential part of the glioblastoma microenvironment. However, in brain tumors the function of these immune cells is not sufficiently clarified. In our study, we investigated differential pro-angiogenic activities of resident microglia and peripheral macrophages and their impact on glioma vascularization and progression. Our data demonstrate stable accumulation of microglia/macrophages during tumor growth. These cells often interact with tumor blood vessels correlating with vascular remodeling. Here, we identified resident microglia as well as peripheral macrophages as part of the perivascular niche, primarily contacting endothelial cells. We found overexpression of a variety of pro-angiogenic molecules within freshly isolated microglia/macrophages from glioma. CXCL2, until now a poorly described chemokine, was strongly up-regulated and showed better angiogenic activity than VEGF in vitro. Blocking the CXCL2-CXCR2 signaling pathway resulted in considerably diminished glioma sizes. Additionally, the importance of microglia/macrophages in tumor angiogenesis was confirmed by depletion of these cells in vivo. Vessel density decreased by 50% leading to significantly smaller tumor volumes. Remarkably, selective reduction of resident microglia affected tumoral vessel count comparable to ablation of the whole myeloid cell fraction. These results provide evidence that resident microglia are the crucial modulatory cell population playing a central role in regulation of vascular homeostasis and angiogenesis in brain tumors. Thus, resident microglia represent an alternative source of pro-angiogenic growth factors and cytokines.
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Registered trials
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