CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

被引：45

作者：

Oue, Erika ^{[2
,3
]}

Lee, Ji-Won

Sakamoto, Kei

Iimura, Tadahiro ^{[3
]}

Aoki, Kazuhiro ^{[4
]}

Kayamori, Kou ^{[5
,6
]}

Michi, Yasuyuki ^{[2
]}

Yamashiro, Masashi ^{[2
]}

Harada, Kiyoshi ^{[2
]}

Amagasa, Teruo ^{[2
]}

Yamaguchi, Akira ^{[1
,3
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Oral Pathol, Bunkyo Ku, Tokyo 1138549, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Maxillofacial Surg, Tokyo 1138549, Japan

[3] Tokyo Med & Dent Univ, Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence GCOE Program, Tokyo 1138549, Japan

[4] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Pharmacol, Tokyo 1138549, Japan

[5] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Diagnost Oral Pathol, Tokyo 1138549, Japan

[6] Ome Municipal Gen Hosp, Dept Pathol, Ome, Tokyo, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 424卷 / 03期

基金：

日本学术振兴会;

关键词：

Oral cancer; CXCL2; Osteoclast; Bone resorption; RANKL; OSTEOCLAST DIFFERENTIATION; MANDIBULAR INVASION; GRO-BETA; IN-VIVO; EXPRESSION; INTERLEUKIN-6; LIGAND; MOUSE; MICE;

D O I：

10.1016/j.bbrc.2012.06.132

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：456 / 461

页数：6

共 21 条

[1]

Functions of RANKL/RANK/OPG in bone modeling and remodeling [J].