The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16
AbstractReverse signaling is a signaling mechanism where transmembrane or membrane-bound ligands transduce signals and exert biological effects upon binding of their specific receptors, enabling a bidirectional signaling between ligand and receptor-expressing cells. In this study, we address the question of whether the transmembrane chemokine (C-X-C motif) ligand 16, CXCL16 is able to transduce reverse signaling and investigate the biological consequences. For this, we used human glioblastoma cell lines and a melanoma cell line as in vitro models to show that stimulation with recombinant C-X-C chemokine receptor 6 (CXCR6) or CXCR6-containing membrane preparations induces intracellular (reverse) signaling. Specificity was verified by RNAi experiments and by transfection with expression vectors for the intact CXCL16 and an intracellularly-truncated form of CXCL16. We showed that reverse signaling via CXCL16 promotes migration in CXCL16-expressing melanoma and glioblastoma cells, but does not affect proliferation or protection from chemically-induced apoptosis. Additionally, fast migrating cells isolated from freshly surgically-resected gliomas show a differential expression pattern for CXCL16 in comparison to slowly-migrating cells, enabling a possible functional role of the reverse signaling of the CXCL16/CXCR6 pair in human brain tumor progression in vivo. View Full-Text
- Supplementary File 1:
ZIP-Document (ZIP, 1735 KB)
Share & Cite This Article
Adamski, V.; Mentlein, R.; Lucius, R.; Synowitz, M.; Held-Feindt, J.; Hattermann, K. The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16. Int. J. Mol. Sci. 2017, 18, 1468.
Adamski V, Mentlein R, Lucius R, Synowitz M, Held-Feindt J, Hattermann K. The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16. International Journal of Molecular Sciences. 2017; 18(7):1468.Chicago/Turabian Style
Adamski, Vivian; Mentlein, Rolf; Lucius, Ralph; Synowitz, Michael; Held-Feindt, Janka; Hattermann, Kirsten. 2017. "The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16." Int. J. Mol. Sci. 18, no. 7: 1468.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.