Abstract 289: Temporal and spatial dynamics of glial cells apolipoprotein E expression in astrocytoma microenvironment

Abstract Introduction: Brain tumors have proven challenging to treat due to the complex and sensitive architecture of the brain. Previous research has shown that GBM cells depend highly on cholesterol uptake, and apolipoprotein E (APOE) is required to transport cholesterol among tissues or cells. APOE is primarily synthesized by astrocytes and has been extensively studied in neurodegenerative diseases. While extensively studied in neurodegenerative diseases, limited studies are focusing on their roles in brain tumor development. Here, we analyzed the temporal and spatial expression of APOE during brain tumor progression in a murine astrocytoma tumor model. Material and method: ALTS1C1 astrocytoma cells were intracranially injected into the mouse brain. The animal was sacrificed, and the left hemisphere, right hemisphere, and tumor tissue were collected for flow cytometry analysis. CD45, CD11b, and GFAP were used to recognize macrophages, microglia, and astrocytes. CD68, TMEM119, and GFAP were used for tissue immunostaining to label macrophages, microglia, and astrocytes, respectively. Results and Discussion: Flow cytometry analysis revealed upregulated APOE in tumor-infiltrating microglia, macrophages, and lymphocytes. GFAPhigh astrocytes displayed lower APOE levels than GFAPlow astrocytes. IHC analysis showed that CD68+ macrophages exhibited higher APOE expression at the tumor edge than normal tissue. On the contrary, GFAP+ astrocytes at the tumor edge displayed a lower APOE signal than the normal tissue. Previous studies have shown the participation of APOE in regulating immune response in various cancers. Further studies to analyze the dynamic change of APOE on the gene expression level with in situ hybridization and the quantification of cholesterol levels in the microenvironment may help uncover their roles in the glioma microenvironment. Conclusion: This study demonstrated that APOE was temporal and spatial differentially expressed in macrophages and astrocytes in the brain tumor microenvironment. Tumor-infiltrating cells showed an elevated APOE expression, while GFAP+ astrocytes expressed reduced APOE levels. Although the mechanism of these alterations remains unclear, this study provides a basis for future studies about the roles of APOE in the brain tumor microenvironment. Citation Format: Ting-Yi Chien, Chi-Shiun Chiang. Temporal and spatial dynamics of glial cells apolipoprotein E expression in astrocytoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 289.