Falter, Johannes and Lohmeier, Annette and Eberl, Petra and Stoerr, Eva-Maria and Koskimaeki, Janne and Falter, Lena and Rossmann, Jakob and Mederer, Tobias and Schmidt, Nils Ole and Proescholdt, Martin (2023) CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (23): 16803. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
In glioblastoma (GBM), the interplay of different immune cell subtypes, cytokines, and/or drugs shows high context-dependencies. Interrelations between the routinely applied dexamethasone (Dex) and microglia remain elusive. Here, we exploited rat organotypic brain slice co-cultures (OBSC) to examine the effects on a rat GBM cell line (S635) outgrowth resulting from the presence of Dex and pretreatment with the colony-stimulating factor receptor 1 (CSF1-R) inhibitor PLX5622: in native OBSC (without PLX5622-pretreatment), a diminished S635 spheroid outgrowth was observable, whereas Dex-treatment enhanced outgrowth in this condition compared to PLX5622-pretreated OBSC. Screening the supernatants of our model with a proteome profiler, we found that CXCL2 was differentially secreted in a Dex- and PLX5622-dependent fashion. To analyze causal interrelations, we interrupted the CXCL2/CXCR2-axis: in the native OBSC condition, CXCR2-blocking resulted in increased outgrowth, in combination with Dex, we found potentiated outgrowth. No effect was found in the PLX5622-pretreated. Our method allowed us to study the influence of three different factors-dexamethasone, PLX5622, and CXCL2-in a well-controlled, simplified, and straight-forward mechanistic manner, and at the same time in a more realistic ex vivo scenario compared to in vitro studies. In our model, we showed a GBM outgrowth enhancing synergism between CXCR2-blocking and Dex-treatment in the native condition, which was levelled by PLX5622-pretreatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLIOMA; glioblastoma; OBSC; dexamethasone; PLX5622; CXCL2; danirixin; navarixin; microglia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurochirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 10:58 |
| Last Modified: | 08 Mar 2024 10:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59142 |
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