ArticleCell stem cell2018
Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression.
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Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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164citing papers in PubMed
15.0field-weighted citation impact, top 1% of its field
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Who cites it
164 citing papers in PubMed, 301 citations in OpenAlex.
- Repeated superselective intraarterial bevacizumab after blood brain barrier disruption for newly diagnosed glioblastoma: a phase I/II clinical trial.Journal of neuro-oncology · 2021Trial
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- Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth.Cell · 2026Article
- Complement C5a/C5aR1 pathway facilitates glioblastoma progression via fostering glioma stem cell-macrophage symbiosis.Journal of neuroinflammation · 2026Article
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- Stress granules restrain ferroptosis by sequestering ferritin.Nature cell biology · 2026Article
- Extracellular Vesicles in the Biology and Liquid Biopsy Diagnostics of Pediatric High-Grade Glioma - Emerging Findings and Opportunities.Journal of extracellular biology · 2026Review
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- Modeling glioblastoma relapse in vitro: a critical journey from 2D models to organ-on-chip alternatives.NPJ precision oncology · 2026Review
- Targeting Tumour Microtubes to Disrupt Glioma Networks.Research square · 2026Article
- Article
- MEG3 in glioma stem cells promotes glioblastoma angiogenesis through FUBP3-mediated VGF expression.Clinical and experimental medicine · 2026Article
- Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.Cancer metastasis reviews · 2026Review
- Primary glioma cell culture: from monolayer to organoids.Protoplasma · 2026Review
- Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Cellular neighborhoods in cancer.Nature cancer · 2026Article
- Review
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Endothelial cells-derived SEMA3G suppresses glioblastoma stem cells by inducing c-Myc degradation.Cell death and differentiation · 2025Article
- Chronic administration of metformin exerts cytostatic and cytotoxic effects via the PP2A-GSK3β-MCL-1 pathway by inhibiting the tmCLIC1 membrane protein in glioblastoma-initiating cells.Journal of experimental & clinical cancer research : CR · 2025Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 6 institutions in 3 countries.
Xiuxing WangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Briana C PragerDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Qiulian WuDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Leo J Y KimDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Ryan C GimpleDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Yu ShiInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing, China.
Kailin YangDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Andrew R MortonDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Wenchao ZhouDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Zhe ZhuDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Elisabeth Anne Adanma ObaraBrain Tumor Biology, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen 2100, Denmark.
Tyler E MillerDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Anne SongDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Sisi LaiDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Christopher G HubertDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Xun JinDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Zhi HuangDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Xiaoguang FangDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Deobrat DixitDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Weiwei TaoDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Kui ZhaiDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Cong ChenDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Zhen DongDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Guoxin ZhangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Stephen M DombrowskiDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Petra HamerlikBrain Tumor Biology, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen 2100, Denmark.
Stephen C MackDepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Shideng BaoDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Jeremy N RichDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA. Electronic address: drjeremyrich@gmail.com.
Cleveland Clinic Lerner College of Medicine · USUniversity of California, San Diego · USCase Western Reserve University · USDanish Cancer Society · DKBaylor College of Medicine · USSouthwest Hospital · CN
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MDynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4MNRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9MClinical and Translational Science Collaborative of ClevelandTL1TR000441 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$2.8MTargeting Ferritin in GlioblastomaR01CA169117 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG, CONNOR, JAMES ROBERT · 2013 to 2017
$2.7MMetabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0MTargeting Brain Tumor Stem Cells Through Novel Therapeutic CombinationsR01CA154130 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2010 to 2014
$1.9MFunctional Inhibition of Deubiquitylase HAUSP to Disrupt Glioblastoma Stem CellsR01CA184090 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2015 to 2019
$1.8MGlioblastoma stem cell-derived pericytes and cancer invasionR01NS091080 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7MUbiquitination and Deubiquitination of c-Myc in GlioblastomaR01NS099175 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7MEnergy Stress in Brain Tumor Initiating Stem CellsR01NS089272 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RICH, JEREMY N · 2014 to 2018
$1.7MStem Cell-Like Glioma Cells in AngiogenesisR01CA129958 · NCI · DUKE UNIVERSITY · PI RICH, JEREMY N · 2008 to 2012
$1.6MIntramural NIH HHS Z99 CA999999NCATS NIH HHS TL1 TR000441NCATS NIH HHS TL1 TR002549NCI NIH HHS F30 CA217065NCI NIH HHS F30 CA217066NCI NIH HHS R01 CA116659NCI NIH HHS R01 CA129958NCI NIH HHS R01 CA154130NCI NIH HHS R01 CA169117NCI NIH HHS R01 CA171652NCI NIH HHS R01 CA184090NCI NIH HHS R35 CA197718NIGMS NIH HHS T32 GM007250NINDS NIH HHS K02 NS047409NINDS NIH HHS R01 NS087913NINDS NIH HHS R01 NS089272NINDS NIH HHS R01 NS091080NINDS NIH HHS R01 NS099175
Abstract
Glioblastoma is the most lethal primary brain tumor; however, the crosstalk between glioblastoma stem cells (GSCs) and their supportive niche is not well understood. Here, we interrogated reciprocal signaling between GSCs and their differentiated glioblastoma cell (DGC) progeny. We found that DGCs accelerated GSC tumor growth. DGCs preferentially expressed brain-derived neurotrophic factor (BDNF), whereas GSCs expressed the BDNF receptor NTRK2. Forced BDNF expression in DGCs augmented GSC tumor growth. To determine molecular mediators of BDNF-NTRK2 paracrine signaling, we leveraged transcriptional and epigenetic profiles of matched GSCs and DGCs, revealing preferential VGF expression by GSCs, which patient-derived tumor models confirmed. VGF serves a dual role in the glioblastoma hierarchy by promoting GSC survival and stemness in vitro and in vivo while also supporting DGC survival and inducing DGC secretion of BDNF. Collectively, these data demonstrate that differentiated glioblastoma cells cooperate with stem-like tumor cells through BDNF-NTRK2-VGF paracrine signaling to promote tumor growth.
Indexed as
Disease ProgressionSignal TransductionBrain NeoplasmsCell DifferentiationGlioblastomaHumansNeoplastic Stem CellsBDNFcancer stem celldifferentiated glioma cellglioblastomaglioma stem cellneurotrophinNTRK2VGF
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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 Socratic graph.