ArticleCell death and differentiation2013
Type-3 metabotropic glutamate receptors regulate chemoresistance in glioma stem cells, and their levels are inversely related to survival in patients with malignant gliomas.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review.Neuro-oncology · 2015Pooled it
- Inhibitory glutamatergic feedback for brain tumor therapy.Medical oncology (Northwood, London, England) · 2026Review
- Pathological neural and immune synapses in glioblastoma progression: mechanisms and therapeutic opportunities.Frontiers in neural circuits · 2026Review
- Article
- Research progress in glioma-related epilepsy (Review).Biomedical reports · 2025Article
- Review
- Role of Glutamate Excitotoxicity in Glioblastoma Growth and Its Implications in Treatment.Cell biology international · 2025Review
- Pharmacological Blockade of Group II Metabotropic Glutamate Receptors Reduces the Incidence of Brain Tumors Induced by Prenatal Exposure to N-ethyl-N-nitrosourea in Rats.Current neuropharmacology · 2025Article
- Metabotropic Glutamate Receptors Type 3 and 5 Feature the "NeuroTransmitter-type" of Glioblastoma: A Bioinformatic Approach.Current neuropharmacology · 2024Article
- A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.Frontiers in oncology · 2024Article
- Genomics and transcriptomic alterations of the glutamate receptors in acute myeloid leukemia.Clinical and translational science · 2023Article
- Aloe-Emodin Overcomes Anti-Cancer Drug Resistance to Temozolomide and Prevents Colony Formation and Migration in Primary Human Glioblastoma Cell Lines NULU and ZAR.Molecules (Basel, Switzerland) · 2023Article
- Neuromodulation for Brain Tumors: Myth or Reality? A Narrative Review.International journal of molecular sciences · 2023Review
- Cytotoxicity Effect of Quinoin, Type 1 Ribosome-Inactivating Protein from Quinoa Seeds, on Glioblastoma Cells.Toxins · 2021Article
- Review
- Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma.Cell death & disease · 2021Article
- Review
- Review
- Negative allosteric modulators of metabotropic glutamate receptor 3 target the stem-like phenotype of glioblastoma.Molecular therapy oncolytics · 2021Article
- mGlu3 receptor regulates microglial cell reactivity in neonatal rats.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug treatment of malignant gliomas is limited by the intrinsic resistance of glioma stem cells (GSCs) to chemotherapy. GSCs isolated from human glioblastoma multiforme (GBM) expressed metabotropic glutamate receptors (mGlu3 receptors). The DNA-alkylating agent, temozolomide, killed GSCs only if mGlu3 receptors were knocked down or pharmacologically inhibited. In contrast, mGlu3 receptor blockade did not affect the action of paclitaxel, etoposide, cis-platinum, and irinotecan. mGlu3 receptor blockade enabled temozolomide toxicity by inhibiting a phosphatidylinositol-3-kinase/nuclear factor-κB pathway that supports the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), an enzyme that confers resistance against DNA-alkylating agents. In mice implanted with GSCs into the brain, temozolomide combined with mGlu3 receptor blockade substantially reduced tumor growth. Finally, 87 patients with GBM undergoing surgery followed by adjuvant chemotherapy with temozolomide survived for longer time if tumor cells expressed low levels of mGlu3 receptors. In addition, the methylation state of the MGMT gene promoter in tumor extracts influenced survival only in those patients with low expression of mGlu3 receptors in the tumor. These data encourage the use of mGlu3 receptor antagonists as add-on drugs in the treatment of GBM, and suggest that the transcript of mGlu3 receptors should be measured in tumor specimens for a correct prediction of patients' survival in response to temozolomide treatment.
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