Article
Expression and function of the chemokine CXCL16 and its receptor CXCR6/BONZO in spinal and vestibular human neuromas
Expression und Funktion des Chemokins CXCL16 und seines Rezeptors CXCR6/BONZO in spinalen und Akustikus-Neurinomen des Menschen
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Authors
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J. Held-Feindt
- Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
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R. Mentlein
- Institut für Anatomie, Christian-Albrechts-Universität zu Kiel, Kiel
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F. Knerlich
- Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
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H.-H. Hugo
- Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
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H. M. Mehdorn
- Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
| Published: | April 11, 2007 |
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Outline
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Objective: Neuromas, also called schwannomas or neurilemmomas, are benign neoplasms of peripheral nerve sheaths. Most of these are termed as intradural extramedullary spinal cord tumours or arise from the neurilemmal sheath of the eighth nerve. The types of symptoms are closely related with the tumour location and size and are characterized by compression of neighbouring structures rather than by invasion of different tissues. The chemokine CXCL16 was originally discovered as scavenger receptor for oxidized LDL and independently as ligand for the CXC-chemokine receptor CXCR6 / Bonzo. CXCL16 was found on macrophages, dendritic cells, endothelial, smooth muscle and glioma cells, while CXCR6 was reported to be expressed on activated T-cells and bone marrow plasma cells.
Methods: CXCL16 and CXCR6 mRNA expression was examined using real-time reverse transcription polymerase chain reaction. Protein expression was determined by immunohistochemistry, confocal microscopy, ELISA and Western blotting techniques. After stimulation of cultivated human neuromas with CXCL16 activation of intracellular signal transduction pathways was investigated by Western blotting. Proliferation assays were performed with the CyQuant method, induction of apoptosis was examined by using caspase-3 activity assays.
Results: We could show that in relation to normal nerve tissue CXCL16 and CXCR6 were overexpressed in human spinal and vestibular neuromas on mRNA and protein level. By using confocal microscopy we could demonstrate that CXCL16 and CXCR6 were not only expressed in S100-positive neuroma cells but also co-localized within the same tumour cell. No immunoreactivity could be observed in CD34- or CD68-positive cell types. CXCL16 stimulation of cultivated neuroma cells induced phosphorylation of the p42/44 MAP kinase, whereas no increase in phosphorylation of Akt could be detected. While CXCL16 did not protected cultivated neuroma cells against camptothecin-mediated apoptosis through down-regulation of caspase-3 activity it promoted proliferation up to 140%. This effect could be reduced by application of the MAP kinase inhibitor U-0126.
Conclusions: These findings provide evidence for the overexpression of CXCL16 and CXCR6 in human neuromas which favours tumour growth by induction of proliferation.
