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Int. J. Mol. Sci. 2017, 18(7), 1468; doi:10.3390/ijms18071468

The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16

1
Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany
2
Department of Anatomy, University of Kiel, D-24118 Kiel, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 31 May 2017 / Revised: 27 June 2017 / Accepted: 6 July 2017 / Published: 8 July 2017
(This article belongs to the Special Issue Regulation of Chemokine-Receptor Interactions and Functions)
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Abstract

Reverse 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
Keywords: chemokine; chemokine receptor; reverse signaling; cellular communication; brain tumor; glioma; tumor cell migration chemokine; chemokine receptor; reverse signaling; cellular communication; brain tumor; glioma; tumor cell migration
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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