SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?
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
Journal: International journal of molecular sciences
2022;23(7):3726
PMID: 35409086
Abstract
["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 -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."]
Address:
Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.; Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany.; Division of Tumor Metabolism and Microenvironment, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Department of Internal Medicine IV, University Hospital Munich, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, 97080 Wuerzburg, Germany.; Nuclear Medicine, Medical Faculty, University of Augsburg, 86156 Augsburg, Germany.; Institute for Anatomy, University of Leipzig, 04103 Leipzig, Germany.; Institute of Pathology, Department of Neuropathology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany.; Luebeck Institute of Experimental Dermatology, University of Luebeck, 23538 Luebeck, Germany.; Institute of Forensic Medicine, University of Wuerzburg, 97080 Wuerzburg, Germany.; Donald B. and Catherine C. Marron Cancer Metabolism Center, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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