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Int J Mol Sci. 2017 Jul 8;18(7). pii: E1468. doi: 10.3390/ijms18071468.

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

Author information

1
Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany. Vivian.adamski@uksh.de.
2
Department of Anatomy, University of Kiel, D-24118 Kiel, Germany. rment@anat.uni-kiel.de.
3
Department of Anatomy, University of Kiel, D-24118 Kiel, Germany. rlucius@anat.uni-kiel.de.
4
Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany. Michael.synowitz@uksh.de.
5
Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany. Janka.held-feindt@uksh.de.
6
Department of Anatomy, University of Kiel, D-24118 Kiel, Germany. k.hattermann@anat.uni-kiel.de.

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.

KEYWORDS:

brain tumor; cellular communication; chemokine; chemokine receptor; glioma; reverse signaling; tumor cell migration

PMID:
28698473
PMCID:
PMC5535959
DOI:
10.3390/ijms18071468
[Indexed for MEDLINE]
Free PMC Article

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