PT Journal
AU Adamski, V
   Mentlein, R
   Lucius, R
   Synowitz, M
   Held-Feindt, J
   Hattermann-Koch, K
TI The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16
SO International journal of molecular sciences
PY 2017
VL 18
IS 7
PU MDPI AG
DI 10.3390/ijms18071468
WP https://macau.uni-kiel.de/receive/macau_mods_00003034
LA en
DE Humans; Glioma; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Receptors, Chemokine; Cell Communication; Signal Transduction; Cell Movement; Phosphorylation; Chemokine CXCL16; Receptors, CXCR6
SN 1661-6596
AB 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.
PI Basel
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