Journal Article

Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-κB pathways and promotes osteoclastogenesis in human oral cancer cells

Chih-Hsin Tang, Jing-Yuan Chuang, Yi-Chin Fong, Ming-Chei Maa, Tzong-Der Way and Chien-Hui Hung

in Carcinogenesis

Volume 29, issue 8, pages 1483-1492
Published in print August 2008 | ISSN: 0143-3334
Published online February 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn045

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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.

Journal Article.  6289 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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