Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Department of Oral Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Japan.
Clin Exp Metastasis. 2013 Feb;30(2):133-42. doi: 10.1007/s10585-012-9518-9. Epub 2012 Jul 31.
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.
唾液腺癌（SGC）经常转移到颈部淋巴结和远处器官。目前，导致 SGC 细胞转移行为的机制尚未完全了解。我们之前证明基质细胞衍生因子-1（SDF-1；也称为 CXCL12）/CXCR4 系统参与了口腔鳞状细胞癌的转移建立。在本研究中，我们研究了 CXCR4 在 SGC 转移行为中的作用。我们通过定量 RT-PCR 和 Western blot 分别检查了人 SGC 细胞系中 CXCR4 mRNA 和蛋白的表达。在 6 个人 SGC 细胞系中，有 5 个细胞系的 CXCR4 mRNA 和蛋白表达频繁上调。这些 SGC 细胞系向 SDF-1 梯度迁移的能力证明了功能性 CXCR4 表达。SDF-1 可快速激活 SGC 细胞系中的细胞外信号调节激酶（ERK）1/2。免疫组织化学分析显示，16 例腺样囊性癌（ACC）和 6 例黏液表皮样癌（MEC）组织中的癌组织中均检测到 CXCR4 蛋白表达，这两种癌组织代表 SGC。此外，ACC 细胞系在静脉接种后表现出明显的肺转移，而 CXCR4 拮抗剂 AMD3100 可显著抑制细胞的肺转移，减轻体重减轻并提高荷瘤裸鼠的存活率。这些结果表明 CXCR4 表达有助于 SGC 的转移潜力。
