ArticleNeuro-oncology2015
Glioma-derived versican promotes tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling.
Open access · bronzeAbstract read
In one paragraph
Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
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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.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives.International journal of molecular sciences · 2022Pooled it
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Chlorpromazine activates cGAS-STING signaling and reprograms the immune response in glioblastoma.Frontiers in immunology · 2026Article
- VCAN is upregulated in the cervical cancer stroma and modulates macrophage polarization.Frontiers in oncology · 2026Article
- Host TLR4 activation by tenascin-C is associated with MMP14-dependent glioma invasion.Frontiers in oncology · 2026Article
- Dysregulated Microglial Synaptic Engulfment in Diffuse Midline Glioma.bioRxiv : the preprint server for biology · 2025Article
- Progenitor cells, microglia, and non-coding RNAs: Orchestrators of glioblastoma pathogenesis and therapeutic resistance.Non-coding RNA research · 2025Review
- In vivo generation of CAR macrophages via the enucleated mesenchymal stem cell delivery system for glioblastoma therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Navigating the brain: Harnessing endogenous cellular hitchhiking for targeting neoplastic and neuroinflammatory diseases.Asian journal of pharmaceutical sciences · 2025Review
- Emerging macrophage-based therapies for cancer: a review of preclinical and clinical advances.Frontiers in immunology · 2025Review
- Brain microenvironment orchestrates highly aggressive tumor variants: current trends and therapeutic approaches.Frontiers in aging neuroscience · 2025Review
- Co-evolution of glioma and immune microenvironment.Journal for immunotherapy of cancer · 2024Review
- Local delivery of doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma.Drug delivery and translational research · 2024Article
- Current approaches in glioblastoma multiforme immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Review
- Review
- Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma.Acta neuropathologica communications · 2024Article
- Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.International journal of molecular sciences · 2024Review
- Novel approaches to targeting gliomas at the leading/cutting edge.Journal of neurosurgery · 2023Review
- Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Mouse Glioblastoma Model.Ultrasound in medicine & biology · 2023Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Feng HuCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Omar Dildar DzayeCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Alexander HahnCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Yong YuCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Rick Joey ScavettaCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Gunnar DittmarCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Adrian Kamil KaczmarekCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Kylie R DunningCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Carmela RicciardelliCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Jan L RinnenthalCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Frank L HeppnerCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Seija LehnardtCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Michael SynowitzCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Susanne A WolfCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Helmut KettenmannCellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany (F.H., O.D.a D., A.H., S.A.W., H.K.); Cancer Genetics and Cellular Stress Responses, Max Delbrück Center for Molecular Medicine, Berlin, Germany (Y.Y.); Mass Spectrometry, Max Delbrück Center for Molecular Medicine, Berlin, Germany (R.J.S., G.D.); Robinson Institute, University of Adelaide, Adelaide, Australia (A.K.K., K.R.D., C.R.); Department of Neuropathology, Charité Medical University, Berlin, Germany (J.L.R., F.L.H.); Department of Neurology and Center for Anatomy, Charité Medical University, Berlin, Germany (S.L.); Department of Neurosurgery, Charité Medical University, 13353 Berlin, Germany (M.S.)Present affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, People's Republic of China (F.H.).
Charité - Universitätsmedizin Berlin · DEMax Delbrück Center · DEUniversity of Adelaide · AU
Funding
Non-neoplastic cell types dictate gliomagenesis andU01CA160882 · NCI · EMORY UNIVERSITY · PI HAMBARDZUMYAN, DOLORES, HOLLAND, ERIC C. · 2012 to 2016
$2.8MNCI NIH HHS U01CA160882-01A1
Abstract
backgroundAccumulation and infiltration of microglia/brain macrophages around and into glioma tissue promote tumor invasion and expansion. One tumor-promoting mechanism of microglia/brain macrophages is upregulation of membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation of extracellular matrix. MT1-MMP upregulation is induced by soluble factors released by glioma cells activating microglial Toll-like receptor 2 (TLR2).
methodsVersican identified by proteomics was silenced in glioma cells by short interference RNA and short hairpin RNA approaches and studied in vitro and after injection into mouse brains or organotypic brain slices.
resultsThe splice variants V0/V1 of the endogenous TLR2 ligand versican are highly expressed in mouse and human glioma tissue. Versican-silenced gliomas induced less MT1-MMP expression in microglia both in vitro and in vivo, which resulted in smaller tumors and longer survival rates as compared with controls. Recombinant versican V1 induced significantly higher levels of MT1-MMP in wild-type microglia compared with untreated and treated TLR2 knockout microglial cells. Using glioma-injected organotypic brain slices, we found that the impact of versican signaling on glioma growth depended on the presence of microglia. Moreover, we found that TLR2 expression is upregulated in glioma-associated microglia but not in astrocytes. Additionally, an established TLR2 neutralizing antibody reduced glioma-induced microglial MT1-MMP expression as well as glioma growth ex vivo.
conclusionsOur results show that versican released from glioma promotes tumor expansion through glioma-associated microglial/macrophage TLR2 signaling and subsequent expression of MT1-MMP. This signaling cascade might be a novel target for glioma therapies.
Indexed as
AnimalsBrain NeoplasmsCell Line, TumorGliomaHumansMacrophagesMatrix Metalloproteinase 1MiceMice, Inbred C57BLMice, KnockoutMicrogliaSignal TransductionSurvival RateToll-Like Receptor 2VersicansMatrix Metalloproteinase 1Tlr2 protein, mouseToll-Like Receptor 2Vcan protein, mouseVersicansgliomamicroglia/brain macrophagesMT1-MMPTLR2versican
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