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Matsumoto, Yuji Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Ichikawa, Tomotsugu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kaken ID researchmap
Kurozumi, Kazuhiko Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kaken ID researchmap
Otani, Yoshihiro Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Fujimura, Atsushi Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID researchmap
Fujii, Kentaro Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Tomita, Yusuke Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Hattori, Yasuhiko Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Uneda, Atsuhito Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Tsuboi, Nobushige Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Kaneda, Keisuke Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Makino, Keigo Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Date, Isao Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Abstract
Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness.
Keywords
ANXA2
OSMR
Invasion
Mesenchymal transition
Glioblastoma
Published Date
2020-04-05
Publication Title
Acta Neuropathologica Communications
Volume
volume8
Issue
issue1
Publisher
BMC
Start Page
42
ISSN
2051-5960
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© The Author(s). 2020
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PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1186/s40478-020-00916-7
License
https://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
17K10866
17K10865