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.
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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) |