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Volume 22
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10.3390/ijms22169028
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Article

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

by
Toya Okawa
1,†,
Kurumi Hara
1,†,
Momoko Goto
1,
Moe Kikuchi
1,
Masataka Kogane
1,
Hiroto Hatakeyama
1,
Hiroki Tanaka
2,
Daiki Shirane
2,
Hidetaka Akita
2,
Akihiro Hisaka
1 and
Hiromi Sato
1,*
1
Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan
2
Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Int. J. Mol. Sci. 2021, 22(16), 9028; https://doi.org/10.3390/ijms22169028
Submission received: 14 June 2021 / Revised: 7 August 2021 / Accepted: 17 August 2021 / Published: 21 August 2021
(This article belongs to the Special Issue Astrocytes: Emerging Roles in the Pathogenesis and Treatment of CNS Disorders 2.0)
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Abstract

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.
Keywords: cGAMP; metabolome shift; astrocyte; metastatic brain tumor; glutamate cGAMP; metabolome shift; astrocyte; metastatic brain tumor; glutamate
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MDPI and ACS Style

Okawa, T.; Hara, K.; Goto, M.; Kikuchi, M.; Kogane, M.; Hatakeyama, H.; Tanaka, H.; Shirane, D.; Akita, H.; Hisaka, A.; et al. Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis. Int. J. Mol. Sci. 2021, 22, 9028. https://doi.org/10.3390/ijms22169028

AMA Style

Okawa T, Hara K, Goto M, Kikuchi M, Kogane M, Hatakeyama H, Tanaka H, Shirane D, Akita H, Hisaka A, et al. Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis. International Journal of Molecular Sciences. 2021; 22(16):9028. https://doi.org/10.3390/ijms22169028

Chicago/Turabian Style

Okawa, Toya, Kurumi Hara, Momoko Goto, Moe Kikuchi, Masataka Kogane, Hiroto Hatakeyama, Hiroki Tanaka, Daiki Shirane, Hidetaka Akita, Akihiro Hisaka, and et al. 2021. "Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis" International Journal of Molecular Sciences 22, no. 16: 9028. https://doi.org/10.3390/ijms22169028

APA Style

Okawa, T., Hara, K., Goto, M., Kikuchi, M., Kogane, M., Hatakeyama, H., Tanaka, H., Shirane, D., Akita, H., Hisaka, A., & Sato, H. (2021). Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis. International Journal of Molecular Sciences, 22(16), 9028. https://doi.org/10.3390/ijms22169028

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