RRC ID 43944
著者 Oue E, Lee JW, Sakamoto K, Iimura T, Aoki K, Kayamori K, Michi Y, Yamashiro M, Harada K, Amagasa T, Yamaguchi A.
タイトル CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction.
ジャーナル Biochem Biophys Res Commun
Abstract To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.
巻・号 424(3)
ページ 456-61
公開日 2012-8-3
DOI 10.1016/j.bbrc.2012.06.132
PII S0006-291X(12)01234-X
PMID 22771802
MeSH Animals Bone Resorption / etiology* Bone Resorption / metabolism* Bone Resorption / pathology Carcinoma, Squamous Cell / complications* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Line, Tumor Chemokine CXCL2 / biosynthesis Chemokine CXCL2 / metabolism* Coculture Techniques Culture Media, Conditioned / chemistry Culture Media, Conditioned / pharmacology Humans Mice Mice, Nude Mouth Neoplasms / complications* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Neoplasm Transplantation Oligonucleotide Array Sequence Analysis Osteoclasts / pathology Osteoprotegerin / metabolism RANK Ligand / biosynthesis
IF 2.985
引用数 20
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 ST2(RCB0224)