글로벌 연구동향
핵의학
- 2023년 09월호
[Biomater Res .] Astrocytic scar restricting glioblastoma via glutamate-MAO-B activity in glioblastoma-microglia assembloid
성상세포성 흉터가 글루타메이트 MAO-B활성화를 통해 뇌종양을 제한하는 기전IBS, 연세의대, 성균관의대 / Yen N Diep, 박희정, 이창준* 윤미진*, 조한상*
- 출처
- Biomater Res .
- 등재일
- 2023 Jul 19
- 저널이슈번호
- 27(1):71. doi: 10.1186/s40824-023-00408-4.
- 내용
Abstract
Background: Glial scar formation is a reactive glial response confining injured regions in a central nervous system. However, it remains challenging to identify key factors formulating glial scar in response to glioblastoma (GBM) due to complex glia-GBM crosstalk.Methods: Here, we constructed an astrocytic scar enclosing GBM in a human assembloid and a mouse xenograft model. GBM spheroids were preformed and then co-cultured with microglia and astrocytes in 3D Matrigel. For the xenograft model, U87-MG cells were subcutaneously injected to the Balb/C nude female mice.
Results: Additional glutamate was released from GBM-microglia assembloid by 3.2-folds compared to GBM alone. The glutamate upregulated astrocytic monoamine oxidase-B (MAO-B) activity and chondroitin sulfate proteoglycans (CSPGs) deposition, forming the astrocytic scar and restricting GBM growth. Attenuating scar formation by the glutamate-MAO-B inhibition increased drug penetration into GBM assembloid, while reducing GBM confinement.
Conclusions: Taken together, our study suggests that astrocytic scar could be a critical modulator in GBM therapeutics.
Affiliations
Yen N Diep # 1 2 3, Hee Jung Park # 4, Joon-Ho Kwon # 5 6, Minh Tran 1 2 3, Hae Young Ko 4, Hanhee Jo 4, Jisu Kim 4, Jee-In Chung 4, Tai Young Kim 5, Dongwoo Kim 4, Jong Hee Chang 7, You Jung Kang 1 2, C Justin Lee 8 9 10, Mijin Yun 11, Hansang Cho 12 13 14
1Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
2Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
3Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
4Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
5Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126, Republic of Korea.
6Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, Ulsan, 44919, Republic of Korea.
7Department of Neurosurgery, Severance Hospital, Seoul, 120-752, Republic of Korea.
8Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126, Republic of Korea. cjl@ibs.re.kr.
9Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, Ulsan, 44919, Republic of Korea. cjl@ibs.re.kr.
10Korea University-Korea Institute of Science and Technology, Graduate School of Convergence Technology, Korea University, Seoul, 136-701, Republic of Korea. cjl@ibs.re.kr.
11Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. YUNMIJIN@yuhs.ac.
12Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
13Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
14Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
#Contributed equally.
- 키워드
- Assembloid; Glial scar formation; Glioblastoma; Glutamate; MAO-B; Microglia.
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