| Autor: |
Löhr, Mario, Härtig, Wolfgang, Schulze, Almut, Kroiß, Matthias, Sbiera, Silviu, Lapa, Constantin, Mages, Bianca, Strobel, Sabrina, Hundt, Jennifer Elisabeth, Bohnert, Simone, Kircher, Stefan, Janaki-Raman, Sudha, Monoranu, Camelia-Maria |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Druh dokumentu: |
Článek |
| Popis: |
Targeting molecular alterations as an effective treatment for isocitrate dehydrogenasewildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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