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Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-κB pathways and promotes osteoclastogenesis in human oral cancer cells
Oral squamous cell carcinoma (SCC) has a striking tendency to invade to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and plays a key role in homing of hematopoietic cells to the bone marrow. Interleukin (IL)-6 plays an important role in osteocla...
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Published in: | Carcinogenesis (New York) 2008-08, Vol.29 (8), p.1483-1492 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Oral squamous cell carcinoma (SCC) has a striking tendency to invade to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and plays a key role in homing of hematopoietic cells to the bone marrow. Interleukin (IL)-6 plays an important role in osteoclastogenesis. Herein, we found that SDF-1α increased the secretion of IL-6 in cultured human SCC cells, as shown by reverse transcriptase–polymerase chain reaction and enzyme-linked immunosorbent assay. SDF-1α also increased the surface expression of chemokine receptor 4 (CXCR4) in SCC cells. CXCR4-neutralizing antibody, CXCR4-specific inhibitor (AMD3100) or small interfering RNA against CXCR4 inhibited SDF-1α-induced increase IL-6 production. The transcriptional regulation of IL-6 by SDF-1α was mediated by phosphorylation of extracellular signal-regulated kinases (ERKs) and activation of the nuclear factor-kappa B (NF-κB) components p65 and p50. The binding of p65 and p50 to the NF-κB element on the IL-6 promoter was enhanced by SDF-1α. In addition, IL-6 antibody antagonized the SCC-conditioned medium-increased osteoclastogenesis. These results suggested that SDF-1α from osteoblasts could induce release of IL-6 in human SCC cells via activation of CXCR4, ERK and NF-κB pathway and thereby promote osteoclastogenesis. |
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ISSN: | 0143-3334 1460-2180 |
DOI: | 10.1093/carcin/bgn045 |