Journal article
Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression
Cell stem cell, Vol.22(4), pp.514-528.e5
04/05/2018
DOI: 10.1016/j.stem.2018.03.011
PMCID: PMC5947947
PMID: 29625067
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.
Details
- Title: Subtitle
- Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression
- Creators
- Xiuxing Wang - University of California, San DiegoBriana C. Prager - Cleveland Clinic Lerner College of MedicineQiulian Wu - University of California, San DiegoLeo J. Y. Kim - Case Western Reserve UniversityRyan C. Gimple - University of California, San DiegoYu Shi - Army Medical UniversityKailin Yang - Cleveland Clinic Lerner College of MedicineAndrew R. Morton - Case Western Reserve UniversityWenchao Zhou - Cleveland Clinic Lerner College of MedicineZhe Zhu - University of California, San DiegoElisabeth Anne Adanma Obara - Danish Cancer SocietyTyler E. Miller - Case Western Reserve UniversityAnne Song - Cleveland Clinic Lerner College of MedicineSisi Lai - Cleveland Clinic Lerner College of MedicineChristopher G. Hubert - Cleveland Clinic Lerner College of MedicineXun Jin - Cleveland Clinic Lerner College of MedicineZhi Huang - Cleveland Clinic Lerner College of MedicineXiaoguang Fang - Cleveland Clinic Lerner College of MedicineDeobrat Dixit - University of California, San DiegoWeiwei Tao - Cleveland Clinic Lerner College of MedicineKui Zhai - Cleveland Clinic Lerner College of MedicineCong Chen - Cleveland Clinic Lerner College of MedicineZhen Dong - University of California, San DiegoGuoxin Zhang - University of California, San DiegoStephen M. Dombrowski - Case Western Reserve UniversityPetra Hamerlik - Danish Cancer SocietyStephen C. Mack - Baylor College of MedicineShideng Bao - Cleveland Clinic Lerner College of MedicineJeremy N. Rich - University of California, San Diego
- Resource Type
- Journal article
- Publication Details
- Cell stem cell, Vol.22(4), pp.514-528.e5
- Publisher
- Elsevier
- DOI
- 10.1016/j.stem.2018.03.011
- PMID
- 29625067
- PMCID
- PMC5947947
- ISSN
- 1934-5909
- eISSN
- 1875-9777
- Number of pages
- 20
- Grant note
- CA197718; CA154130; CA169117; CA171652; NS087913; NS089272; CA184090; NS091080; NS099175 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 04/05/2018
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696709302771
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