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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Eibinger, G; Fauler, G; Bernhart, E; Frank, S; Hammer, A; Wintersperger, A; Eder, H; Heinemann, A; Mischel, PS; Malle, E; Sattler, W.
On the role of 25-hydroxycholesterol synthesis by glioblastoma cell lines. Implications for chemotactic monocyte recruitment.
Exp Cell Res. 2013; 319(12):1828-1838 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Eder Hans
Eibinger Gerald
Fauler Günter
Frank Saša
Hammer Astrid
Heinemann Akos
Malle Ernst
Sattler Wolfgang
Wintersperger Andrea
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Number of Figures: 7
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Abstract:
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor and is invariably fatal to affected patients. Oxysterols belong to a class of bioactive lipids that are implicated in neurological disease and are associated with various types of cancer. Here, we investigated expression and transcriptional regulation of cholesterol 25-hydroxylase (CH25H) in human U87MG and GM133 glioblastoma cell lines. We demonstrate that in both cell lines transcription and translation of CH25H are increased in response to TNFα and IL1β. In parallel, both cell lines upregulate 25-hydroxycholesterol (25-OHC) synthesis and secretion to levels comparable to bone marrow-derived mouse macrophages under inflammatory conditions. To determine whether 25-OHC acts as chemoattractant for tumor-associated macrophages, the human THP-1 monoblastic leukemia cell line was treated with varying amounts of the oxysterol. Experiments revealed that 25-OHC and lipid extracts isolated from GM133-conditioned medium (containing 7-fold higher 25-OHC concentrations than U87MG medium) induce chemotactic migration of THP-1 cells. Of note, 25-OHC also induced the migration of primary human peripheral blood monocytes. In response to exogenously added 25-OHC, THP-1 cells reorganized intermediate filament-associated vimentin to more cortical and polarized structures. Chemotactic migration of monocytes in response to 25-OHC was pertussis toxin-sensitive, indicating the involvement of G protein-coupled receptors. Using RNA interference we demonstrated that G protein-coupled receptor 183 (EBI2) contributes to 25-OHC-mediated chemotactic migration of THP-1 cells. These in vitro data indicate that GBM-derived and secreted 25-OHC may be involved in the recruitment of immune-competent cells to a tumor via EBI2.
Find related publications in this database (using NLM MeSH Indexing)
Brain Neoplasms - metabolism
Cell Line, Tumor -
Chemotaxis - drug effects
Glioblastoma - metabolism
Humans -
Hydroxycholesterols - metabolism
Monocytes - physiology
Protein Biosynthesis -
RNA, Small Interfering -
Receptors, G-Protein-Coupled - genetics
Steroid Hydroxylases - genetics
Sterols - pharmacology
Transcription, Genetic -
Up-Regulation -
Vimentin - metabolism

Find related publications in this database (Keywords)
EBI2
Migration
Glioblastoma
TNF alpha
IL1 beta
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