Molecular analysis of bone invasion mechanism in oral carcinoma.

我们用微阵列技术研究了口腔鳞状细胞癌(OSCC)中的骨侵袭。对口腔鳞状细胞癌标本进行的基因芯片分析显示，许多标本过表达PTHrP mRNA，但少数标本过表达IL-6。免疫组织化学分析表明，IL-6不仅在癌细胞中表达，而且在肿瘤-骨界面处的成纤维细胞和破骨细胞中也有表达。将HSC3细胞移植到裸鼠顶骨骨膜区域，其组织学和RANKL和IL-6的表达谱与骨侵袭性人类口腔鳞状细胞癌标本相似。这些结果表明，口腔鳞状细胞癌不仅通过产生IL-6和PTHrP，而且通过刺激基质细胞合成IL-6，为破骨细胞的形成提供了合适的微环境。由于口腔鳞癌基因芯片分析中FADD的表达上调和口腔鳞癌细胞系中11q13.3的扩增在比较基因组杂交数据库中已经被…更多的可用，基因组扩增和FADD的表达水平被研究。FADD的DNA扩增阳性率为44.3%，且与鳞癌的分化程度密切相关。FADD的表达水平与配对的相邻上皮相比显著增加。此外，FADD的阳性表达与SCC的淋巴转移和5年生存率显著相关。因此，表达FADD的SCC细胞可能更有可能发生转移并降低存活率。正如前面提到的，FADD在细胞凋亡和增殖中都是从细胞表面受体传递信号所必需的。因此，过去对FADD的研究大多局限于其在细胞质内的功能；然而，最近的研究表明，FADD既位于细胞核中，也位于细胞质中。在这项研究中，口腔鳞状细胞中FADD的免疫反应模式清楚地表明了主要的核定位模式。由于FADD在细胞核中的功能尚未阐明，目前正在研究FADD在细胞核中的有意义的定位。较少

We investigated the bone invasion in oral squamous cell carcinoma (OSCC) using microarray analyses. Microarray analyses performed on human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6. As the up-regulation of FADD expression in OSCC microarray analyses and the amplification of 11q13.3 in oral SCC cell lines on the Comparative Genomic Hybridization (CGH) database have be … More come available, genomic amplifications and expression levels of FADD were investigated. The DNA amplifications of FADD were observed in 44.3% cases and were significantly correlated with the histopathological differentiation grade of SCCs. FADD expression levels compared with the matched adjacent epithelium increased significantly. Additionally, the positive expressions of FADD were significantly correlated with lymph node metastasis of SCCs and the 5-year diseasespecific survival rates. Thus, SCC cells with the expression of FADD are possibly more likely to become metastatic and to worsen survival rates. As previously mentioned, FADD is imperative for transmitting signals from cell surface receptors in both cell apoptosis and proliferation. Therefore, many past studies investigating FADD were confined to its function within the cytoplasm; however, recent studies have demonstrated that FADD is located in both the nucleus and the cytoplasm. In this study, the immunoreactivity pattern of FADD in oral SCCs clearly demonstrated a predominant nuclear localization pattern. As the function of FADD in the nucleus has not been clarified, a meaningful localization of FADD in the nucleus is currently under investigation. Less