Expression and function of CXCR4 in human salivary gland cancers
Expression and function of CXCR4 in human salivary gland cancers
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DOI：
10.1007/s10585-012-9518-9
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发表时间：
2013-02-01
影响因子：
4
通讯作者：
Miyamoto, Youji
中科院分区：
文献类型：
--
作者：
Uchida, Daisuke;Kuribayashi, Nobuyuki;Miyamoto, Youji
唾液腺癌（SGCs）经常转移到颈部淋巴结和远处器官。目前，负责SGC细胞转移行为的机制尚未完全了解。我们以前证明，基质细胞衍生因子-1（SDF-1;也称为CXCL 12）/CXCR 4系统参与口腔鳞状细胞癌转移的建立。在本研究中，我们研究了CXCR 4在SGCs转移行为中的作用。采用RT-PCR和Western blotting方法分别检测人胃癌细胞系CXCR 4 mRNA和蛋白的表达。CXCR 4 mRNA和蛋白表达在6个SGC细胞系中有5个上调。通过这些SGC细胞系向SDF-1梯度迁移的能力证明了功能性CXCR 4表达。SDF-1在SGC细胞系中快速激活细胞外信号调节激酶（ERK）1/2。免疫组化结果显示，在20例腺样囊性癌（adenoid cystic carcinoma，ACC）和6例粘液表皮样癌（mucoepidermoid carcinoma，SGC）组织中，CXCR 4蛋白表达于癌细胞的胞核或胞浆中。此外，ACC细胞株显示出显着的肺转移后，静脉接种，而AMD 3100，CXCR 4拮抗剂，显着抑制细胞的肺转移，改善体重减轻，提高荷瘤裸鼠的生存率。这些结果表明，CXCR 4表达有助于SGCs的转移潜力。
Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and distant organs. Currently, the mechanisms responsible for the metastatic behavior of SGC cells are not fully understood. We previously demonstrated that the stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral squamous cell carcinoma. In the present study, we investigated the role of CXCR4 in the metastatic behavior of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell lines by quantitative RT-PCR and western blotting, respectively. The expression of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell lines. Functional CXCR4 expression was demonstrated by the ability of these SGC cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines. Immunohistochemical analysis revealed that CXCR4 protein expression was detected in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited dramatic metastasis to the lung following intravenous inoculation, whereas AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the cells, ameliorated body weight loss and improved the survival rate of tumor-bearing nude mice. These results indicate that CXCR4 expression contributes to the metastatic potential of SGCs.