한빛사논문
- 조회478
Dongwoo Kim 1, Hae Young Ko 1, Jee-In Chung 1, Yongmin Mason Park 2,3, Sangwon Lee 1, Seon Yoo Kim 1, Jisu Kim 1, Joong-Hyun Chun 1, Kyung-Seok Han 4, Misu Lee 5, Yeon Ha Ju 2,3,6, Sun Jun Park 6,7, Ki Duk Park 6,7, Min-Ho Nam 6,7,8, Se Hoon Kim 9, Jin-Kyoung Shim 10, Youngjoo Park 11, Hyunkeong Lim 1, Jaekyung Park 1, Hyunjin Kim 6, Suhyun Kim 12, Uiyeol Park 12, Hoon Ryu 12, So Yun Lee 13, Sunghyouk Park 13, Seok-Gu Kang 10, Jong Hee Chang 10, C Justin Lee 2,3, Mijin Yun 1
1Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine; Seoul 03722, Republic of Korea.
2Center for Cognition and Sociality, Institute for Basic Science; Daejeon 34126, Republic of Korea.
3IBS School, University of Science and Technology; Daejeon 34126, Republic of Korea.
4Department of Biological Sciences, Chungnam National University; Daejeon 34134, Republic of Korea.
5Division of Life Science, College of Life Science and Bioengineering, Incheon National University; Incheon 22012, Republic of Korea.
6Brain Science Institute, Korea Institute of Science and Technology (KIST); Seoul 02792, Republic of Korea.
7Division of Bio-Med Science & Technology, KIST School, Korea University of Science and Technology; Seoul 02792, Republic of Korea.
8Department of KHU-KIST Convergence Science and Technology, Kyung Hee University; Seoul 02447, Republic of Korea.
9Department of Pathology, Severance Hospital, Yonsei University College of Medicine; Seoul 03722, Republic of Korea.
10Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine; Seoul 03722, Republic of Korea.
11Yonsei University College of Medicine; Seoul 03722, Republic of Korea.
12K-Laboratory, Brain Science Institute, Korea Institute of Science and Technology (KIST); Seoul 02792, Republic of Korea.
13Natural Products Research Institute, College of Pharmacy, Seoul National University; Seoul 08826, Republic of Korea.
Corresponding: Seok-Gu Kang, Jong Hee Chang, C Justin Lee, Mijin Yun
Abstract
Background
Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores 11C-acetate PET as an imaging technique for detecting reactive astrogliosis.
Methods
Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and MCT1 expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis.
Results
Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with worse prognosis.
Conclusion
Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.
논문정보
- Research article
- 2023년 12월 (BRIC 등록일 2023-12-13)
- 국내 연구진
- 의약학 > 응용의학
관련 보도자료
- Bio통신원
- 2024. 01. 16
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