CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction
CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction
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DOI：
10.1016/j.bbrc.2012.06.132
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发表时间：
2012-08-03
影响因子：
3.1
通讯作者：
Yamaguchi, Akira
中科院分区：
文献类型：
--
作者：
Oue, Erika;Lee, Ji-Won;Yamaguchi, Akira
为了探讨口腔癌骨破坏的机制，我们确定了刺激口腔鳞状细胞癌骨吸收的因素。从母体口腔癌细胞系HSC 3中分离出两种克隆细胞系HSC 3-C13和HSC 3-C17。与母体HSC 3细胞和HSC 3-C17细胞相比，来自HSC 3-C13细胞的条件培养基在小鼠基质细胞系ST 2和UAMS-32中显示出对Rankl表达的最高诱导，母体HSC 3细胞和HSC 3-C17细胞显示出相似的活性。HSC 3-C13细胞的条件培养基在与小鼠骨髓细胞和UAMS-32细胞的共培养中显著增加破骨细胞的数量。从这些克隆细胞系产生的异种移植肿瘤进入无胸腺小鼠顶骨的骨膜区域显示，HSC 3-C13细胞引起广泛的骨破坏和破骨细胞数量的显着增加相比，HSC 3-C17细胞。通过使用微阵列分析比较HSC 3-C13和HSC 3-C17细胞之间的基因表达，结果显示，与HSC 3-C17细胞相比，CXCL 2基因在HSC 3-C13细胞中高表达。免疫组化染色显示CXCL 2在人口腔鳞状细胞癌中的定位。通过在共培养系统中加入抗人CXCL 2中和抗体，HSC 3-C13条件培养基诱导的破骨细胞数量的增加被剂量依赖性地抑制。重组CXCL 2增加了UAMS-32细胞中Rankl的表达。这些结果表明，CXCL 2参与口腔癌诱导的骨破坏。这是第一份显示CXCL 2在癌症相关骨破坏中的作用的报告。(C)2012 Elsevier Inc. All rights reserved.
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.