Heterogeneous expression of the atypical chemokine receptor ACKR3 in glioblastoma patient-derived tissue samples and cell cultures

Damla Isci, Amandine Kuppens, Joshua Scalisi, Julie Cokaiko, Giulia D'Uonnolo, May Wantz, Martyna Szpakowska, Andy Chevigné, Bernard Rogister, Virginie Neirinckx*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Glioblastoma (GBM) is the most aggressive glial tumor of the adult brain, associated with invariably fatal outcome, and a deeper understanding of the underlying malignant mechanisms is necessary to address the current therapeutic failure. We previously demonstrated the role of the CXCL12/CXCR4 axis in GBM cell migration and resistance to ionizing radiation. The atypical chemokine receptor ACKR3, responsible for CXCL12 scavenging, was previously suggested as additional important player in the context of GBM. Following validation of the detection tools, we observed that ACKR3 is expressed within GBM patient tumor tissue, distributed in diverse cell types. In contrast to CXCR4, ACKR3 expression in patient-derived stem-like cells (GSCs) remains however low, while ACKR3 gene expression by tumor cells appears to be modulated by the in-vivo environment. Using overexpression models, we also showed that in vitro ACKR3 had no significant direct effect on cell proliferation or invasion. Altogether, these results suggest that in vitro ACKR3 plays a minor role in malignant GBM cell biology and that its expression is possibly regulated by in-vivo influences. The subtle and multifaceted functions ACKR3 could exert in GBM should therefore only be tackled within a comprehensive tumor microenvironment considering tumoral but also non-tumoral cells.

Original languageEnglish
Article number21925
JournalScientific Reports
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • ACKR3
  • Chemokines receptors
  • CXCR7
  • Glioblastoma

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