@Article{macau_mods_00003034, author = {Adamski, Vivian and Mentlein, Rolf and Lucius, Ralph-Erich and Synowitz, Michael and Held-Feindt, Janka and Hattermann-Koch, Kirsten}, title = {The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane Chemokine CXCL16}, journal = {International journal of molecular sciences}, year = {2017}, publisher = {MDPI AG}, address = {Basel}, volume = {18}, number = {7}, keywords = {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}, 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.}, issn = {1661-6596}, doi = {10.3390/ijms18071468}, url = {https://macau.uni-kiel.de/receive/macau_mods_00003034}, url = {https://doi.org/10.3390/ijms18071468}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28698473}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00004181/ijms-18-01468.pdf:PDF}, language = {en} }