腫瘍放出因子cGAMPがアストロサイトの遺伝子発現とカルシウム応答に与える影響

抄録

【Purpose】

Metastatic brain tumors emit various components, including cyclic 2'3'-GMP-AMP (cGAMP) to surrounding astrocytes, which may affect the tumor microenvironments. To identify the cGAMP targets, we analyzed transcriptome in cGAMP-incorporated astrocytes.

【Method】

cGAMP is encapsulated in lipid nanoparticles (ssPalm), then introduced into primary cultured astrocytes. After extracting the RNA, the fold change (FC) by cGAMP was investigated by microarray. Among the genes with high intrinsic expression levels, we searched for interacting factors with large FC in STRING's protein-protein interaction database. As an indicator of astrocyte responsiveness, changes in intracellular calcium concentration were observed by confocal time-lapse imaging.

【Result/Discussion】

As candidates of cGAMP targets, interferon-stimulated genes were determined, such as Viperin and Usp18. Cholecystokinin (CCK), which was reported to be involved in glutamate secretion, showed the largest FC(318-fold). Further, the intracellular calcium concentration increased when CCK was added to astrocytes. We have previously demonstrated that the introduction of cGAMP alters glutamine-glutamate metabolism in astrocytes. We continue to be interested in how these changes relate to each other and contribute to the malignant transformation of metastatic brain tumors.