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

URN zum Zitieren dieses Dokuments:

urn:nbn:de:bvb:355-epub-551630 Copy

DOI zum Zitieren dieses Dokuments:

10.5283/epub.55163 Copy

Falter, Johannes ; Lohmeier, Annette ; Eberl, Petra ; Stoerr, Eva-Maria ; Koskimäki, Janne ; Falter, Lena ; Rossmann, Jakob ; Mederer, Tobias ; Schmidt, Nils Ole ; Proescholdt, Martin A.

Lizenz: Creative Commons Namensnennung 4.0 International PDF - Veröffentlichte Version (4MB)

Veröffentlichungsdatum dieses Volltextes: 05 Dez 2023 10:33

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Details

Dokumentenart:	Artikel
Open Access Art:	Gold (mit APC - bezahlt UR)
Höhe Gebühr (aus OpenAPC):	2771.45
Institution der Zahlung:	Regensburg U
Titel eines Journals oder einer Zeitschrift:	International Journal of Molecular Sciences
Verlag:	MDPI
Band:	24
Nummer des Zeitschriftenheftes oder des Kapitels:	23
Seitenbereich:	S. 16803
Datum:	27 November 2023
Institutionen:	Medizin > Lehrstuhl für Neurochirurgie
Sonstige Projekte:	Else-Kröner-Fresenius Stiftung (project number 3752914)
Identifikationsnummer:	Wert Typ 10.3390/ijms242316803 DOI
Stichwörter / Keywords:	glioblastoma; OBSC; dexamethasone; PLX5622; CXCL2; danirixin; navarixin; microglia
Dewey-Dezimal-Klassifikation:	600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
Status:	Veröffentlicht
Begutachtet:	Ja, diese Version wurde begutachtet
An der Universität Regensburg entstanden:	Ja
Dokumenten-ID:	55163

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Zusammenfassung

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 ...

Zusammenfassung

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.

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