ArticleCarcinogenesis2016
Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.
Article in Carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 63 citations in OpenAlex.
- Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients.NeuroImage. Clinical · 2020Trial
- Review
- NF-κB signaling pathway mediates the anti-tumor effect of Ginsenoside Rg1 in glioblastoma.Biochemistry and biophysics reports · 2026Article
- NHE1-Mediated Metabolic Reprogramming in Cancer.Metabolites · 2026Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Review
- Targeting glioma-associated microglia and macrophages: a new frontier in glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma.International journal of molecular sciences · 2024Review
- Neuroinflammation in Glioblastoma: The Role of the Microenvironment in Tumour Progression.Current cancer drug targets · 2024Review
- Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells.Journal of molecular neuroscience : MN · 2023Article
- Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment.Cellular and molecular neurobiology · 2023Review
- Microglia and Brain Macrophages as Drivers of Glioma Progression.International journal of molecular sciences · 2022Review
- Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes.Neurosurgical focus · 2022Article
- How Reciprocal Interactions Between the Tumor Microenvironment and Ion Transport Proteins Drive Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Research Progress on Improving the Efficiency of CDT by Exacerbating Tumor Acidification.International journal of nanomedicine · 2022Review
- Sodium MR Neuroimaging.AJNR. American journal of neuroradiology · 2021Review
- Macrophages/Microglia in the Glioblastoma Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Advances in research on the regulatory mechanism of NHE1 in tumors.Oncology letters · 2021Review
- Ion channels and transporters in microglial function in physiology and brain diseases.Neurochemistry international · 2021Review
- Targeting the pH Paradigm at the Bedside: A Practical Approach.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia-glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1(+) microglia in glioma xenografts and glioblastoma multiforme microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-β, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via small interfering RNA (siRNA) knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma-microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation.
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What OpenQuestion holds
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.