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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89202 |
| Date | 23 January 2024 |
| Creators | 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 |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 3726 |
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