gms | German Medical Science

70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

Inhibition of CXCR2/CXCL2 signalling pathway in glioblastoma multiforme as a therapeutic approach

Blockade des CXCR2/CXCL2 Signalweges im Glioblastom als therapeutischer Ansatz

Meeting Abstract

  • presenting/speaker Güliz Acker - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Julia Zollfrank - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Claudius Jelgersma - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Susan Brandenburg - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Peter Vajkoczy - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocV196

doi: 10.3205/19dgnc211, urn:nbn:de:0183-19dgnc2110

Veröffentlicht: 8. Mai 2019

© 2019 Acker et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Signaling via CXCR2 and its ligands CXCL2 and CXCL8 is a crucial part of angiogenesis in glioblastoma. The aim of our study was to block this signaling pathway via CXCR2-Antagonist SB225002 as a new therapeutic approach to slow down tumor growth and to analyze the proliferation and altered gene expression after SB225002 treatment in vitro.

Methods: GL261 glioma cells were implanted intracranially in C57/B6N mice. The 14 or 7 day period of intrathecal treatment with SB225002 via a mini osmotic pump was initiated on the day of tumor cell implantation or after 14 days of tumor growth, respectively. The control group received placebo dilution (n=6–7 per group). Tumor volume was verified using MRI before and after the treatment period. Immunofluorescence staining was performed on the tumor tissue with focus on angiogenesis and microglia. Furthermore, glioma cells and, for comparison, endothelial cells were treated in vitro with the antagonist. Proliferation was measured in different concentrations in MTT assays and change in gene expression was detected in real-time PCR. Students t-Test was applied to compare both groups.

Results: Treatment with SB225002 led to a significantly reduced tumor volume of 45% after initial CXCR2-blocking (control: 1,72 mm3±0,53; antagonist: 0,84 mm3±0,35; p=<0,05) and of 46% after blocking the receptor during the exponential tumor growth period (control: 22,17 mm3±8,72; antagonist: 11,70 mm3±3,60; p=<0,05). The immunostainings showed significantly reduced number of microglial cells and vessels in the tumor, an increased interaction of microglia cells with vessels and a consistent CXCL2 expression. The vessel configuration in the healthy brain hemisphere was not altered. Proliferation in vitro was gradually reduced through increasing concentration of antagonist. The decline of proliferation was significantly higher in glioma cells compared to endothelial cells. The gene expression of CXCL2 was increased after SB225002 treatment on GL261 cells in vitro.

Conclusion: The CXCR2 antagonist SB225002 slowed down glioblastoma growth during tumor initiation and growth phase, thus it represents a promising therapeutic agent. The in vivo results were consistent in cell culture experiments with suppression of the proliferation in glioma cells and an upregulation of key points in CXCR2/CXCL2 signaling pathway. Further investigations are needed to clarify more of the underlying molecular pathways and to establish a systemic application.