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SOAT1: A suitable target for therapy in high-grade astrocytic glioma?
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-284178
- Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype 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 theTargeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype 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.…
Autor(en): | Mario Löhr, Wolfgang Härtig, Almut Schulze, Matthias Kroiß, Silviu Sbiera, Constantin Lapa, Bianca Mages, Sabrina Strobel, Jennifer Elisabeth Hundt, Simone Bohnert, Stefan Kircher, Sudha Janaki-Raman, Camelia-Maria Monoranu |
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URN: | urn:nbn:de:bvb:20-opus-284178 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik |
Medizinische Fakultät / Institut für Rechtsmedizin | |
Medizinische Fakultät / Pathologisches Institut | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik I | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 23 |
Heft / Ausgabe: | 7 |
Aufsatznummer: | 3726 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2022) 23:7, 3726. DOI:10.3390/ijms23073726 |
DOI: | https://doi.org/10.3390/ijms23073726 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | IDH1/2; SOAT1; astrocytoma; glioblastoma; lipid droplets; mitotane; targeted therapy |
Datum der Freischaltung: | 11.04.2023 |
Datum der Erstveröffentlichung: | 28.03.2022 |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |