Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea.
Neuro Oncol. 2024 May 3;26(5):843-857. doi: 10.1093/neuonc/noad243.
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 explore 11C-acetate PET as an imaging technique for detecting reactive astrogliosis.
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 monocarboxylate transporter 1 (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.
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 a worse prognosis.
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.
反应性星形胶质细胞增生是各种脑病理学的标志，包括神经退行性疾病和胶质母细胞瘤。然而，导致反应性星形胶质细胞增生的特定中间代谢物仍不清楚。本研究调查了胶质母细胞瘤如何在邻近的微环境中诱导反应性星形胶质细胞增生，并探讨了 11C-乙酸 PET 作为检测反应性星形胶质细胞增生的成像技术。
通过体外、小鼠模型和人体组织实验，我们研究了升高的 11C-乙酸摄取与胶质瘤中反应性星形胶质细胞增生之间的关联。我们研究了来自胶质母细胞瘤细胞的乙酸，通过上调 MAO-B 和单羧酸转运蛋白 1（MCT1）的表达，触发邻近星形胶质细胞的反应性星形胶质细胞增生。我们评估了胶质母细胞瘤反应性星形胶质细胞区域中癌症干细胞的存在，并评估了 MRI 以外的 11C-乙酸摄取量与预后之间的相关性。
在人类组织和小鼠模型中，升高的 11C-乙酸摄取与胶质母细胞瘤周围的反应性星形胶质细胞和星形胶质细胞 MCT1 相关。由于葡萄糖代谢，胶质母细胞瘤细胞产生更多的乙酸，随后乙酸分泌。来自胶质母细胞瘤细胞的乙酸通过增加 MAO-B 和 MCT1 的表达，诱导邻近星形胶质细胞的反应性星形胶质细胞增生。我们在肿瘤边缘的反应性星形胶质细胞中发现了癌症干细胞。因此，MRI 以外的 11C-乙酸摄取量较大与预后较差相关。
我们的结果强调了来自胶质母细胞瘤细胞的乙酸在诱导反应性星形胶质细胞增生中的作用，并强调了 11C-乙酸 PET 作为检测反应性星形胶质细胞增生的成像技术的潜在价值，为胶质母细胞瘤的诊断和治疗提供了重要意义。
