Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis

• Main Authors: Toya Okawa, Kurumi Hara, Momoko Goto, Moe Kikuchi, Masataka Kogane, Hiroto Hatakeyama, Hiroki Tanaka, Daiki Shirane, Hidetaka Akita, Akihiro Hisaka, Hiromi Sato
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: cGAMP; metabolome shift; astrocyte; metastatic brain tumor; glutamate
• Online Access: https://www.mdpi.com/1422-0067/22/16/9028
• ISSN: 1661-6596; 1422-0067

The second messenger 2′3′-cyclic-GMP-AMP (cGAMP) is thought to be transmitted from brain carcinomas to astrocytes via gap junctions, which functions to promote metastasis in the brain parenchyma. In the current study, we established a method to introduce cGAMP into astrocytes, which simulates the state of astrocytes that have been invaded by cGAMP around tumors. Astrocytes incorporating cGAMP were analyzed by metabolomics, which demonstrated that cGAMP increased glutamate production and astrocyte secretion. The same trend was observed for γ-aminobutyric acid (GABA). Conversely, glutamine production and secretion were decreased by cGAMP treatment. Due to the fundamental role of astrocytes in regulation of the glutamine–glutamate cycle, such metabolic changes may represent a potential mechanism and therapeutic target for alteration of the central nervous system (CNS) environment and the malignant transformation of brain carcinomas.