ArticleCell communication and signaling : CCS2020
Extracellular vesicles originating from glioblastoma cells increase metalloproteinase release by astrocytes: the role of CD147 (EMMPRIN) and ionizing radiation.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Pooled it
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Mammary Fibroblasts Secrete Damage Associated Molecular Patterns Through Extracellular Vesicles in Response to Ionizing Radiation.Journal of extracellular biology · 2026Article
- Role of matrix metalloproteinases in the invasion of glioblastoma and drug interventions (Review).International journal of molecular medicine · 2026Review
- Extracellular vesicles as nanocarriers in glioblastoma: implications for chemoresistance and immune evasion.Frontiers in molecular neuroscience · 2026Review
- AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles.Molecular and cellular neurosciences · 2025Article
- Extracellular vesicles released by glioblastoma cancer cells drive tumor invasiveness via Connexin-43 gap junctions.Neuro-oncology · 2025Article
- Deciphering the Dialogue between Brain Tumors, Neurons, and Astrocytes.The American journal of pathology · 2025Review
- Distinct astrocyte activation patterns associated with neuroinflammation induced by gamma and proton beam irradiation.Scientific reports · 2025Article
- CD147-expressed small extracellular vesicles enhance the detection of colorectal neoplasia with fecal immunochemical test.ESMO gastrointestinal oncology · 2025Article
- Nano-Drug Delivery Systems Targeting MMPs: A Promising Treatment for Gliomas.International journal of nanomedicine · 2025Review
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.BMC medicine · 2024Review
- Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells.Neurology international · 2024Article
- The Interplay between Glioblastoma Cells and Tumor Microenvironment: New Perspectives for Early Diagnosis and Targeted Cancer Therapy.Brain sciences · 2024Review
- Deciphering the CNS-glioma dialogue: Advanced insights into CNS-glioma communication pathways and their therapeutic potential.Journal of central nervous system disease · 2024Review
- Optimizing CAR-T Therapy for Glioblastoma.Molecular diagnosis & therapy · 2023Review
- Extracellular Vesicles Potentiate Medulloblastoma Metastasis in an EMMPRIN and MMP-2 Dependent Manner.Cancers · 2023Article
- Roles of extracellular vesicles in glioblastoma: foes, friends and informers.Frontiers in oncology · 2023Review
- Recent advances in label-free optical, electrochemical, and electronic biosensors for glioma biomarkers.Biomicrofluidics · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlioblastoma multiforme is an aggressive primary brain tumor that is characterized by local invasive growth and resistance to therapy. The role of the microenvironment in glioblastoma invasiveness remains unclear. While carcinomas release CD147, a protein that signals for increased matrix metalloproteinase (MMP) release by fibroblasts, glioblastoma does not have a significant fibroblast component. We hypothesized that astrocytes release MMPs in response to CD147 contained in glioblastoma-derived extracellular vesicles (EVs) and that ionizing radiation, part of the standard treatment for glioblastoma, enhances this release.
methodsAstrocytes were incubated with EVs released by irradiated or non-irradiated human glioblastoma cells wild-type, knockdown, or knockout for CD147. Levels of CD147 in glioblastoma EVs and MMPs secreted by astrocytes were quantified. Levels of proteins in the mitogen activated protein kinase (MAPK) pathway, which can be regulated by CD147, were measured in astrocytes incubated with EVs from glioblastoma cells wild-type or knockdown for CD147. Immunofluorescence was performed on the glioblastoma cells to identify changes in CD147 localization in response to irradiation, and to confirm uptake of the EVs by astrocytes.
resultsImmunoblotting and mass spectrometry analyses showed that CD147 levels in EVs were transiently increased when the EVs were from glioblastoma cells that were irradiated with γ rays. Specifically, the highly-glycosylated 45 kDa form of CD147 was preferentially present in the EVs relative to the cells themselves. Immunofluorescence demonstrated that astrocytes incorporate glioblastoma EVs and subsequently increase their secretion of active MMP9. The increase was greater if the EVs were from irradiated glioblastoma cells. Testing MAPK pathway activation, which also regulates MMP expression, showed that JNK signaling, but not ERK1/2 or p38, was increased in astrocytes incubated with EVs from irradiated compared to non-irradiated glioblastoma cells. Knockout of CD147 in glioblastoma cells blocked the increased JNK signaling and the rise in secreted active MMP9 levels.
conclusionsThe results support a tumor microenvironment-mediated role of CD147 in glioblastoma invasiveness, and reveal a prominent role for ionizing radiation in enhancing the effect. They provide an improved understanding of glioblastoma intercellular signaling in the context of radiotherapy, and identify pathways that can be targeted to reduce tumor invasiveness. Video abstract.
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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 OpenQuestion graph.