First Department of Oral and Maxillofacial Surgery, School of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China.
Oral Oncol. 2009 Jun;45(6):480-5. doi: 10.1016/j.oraloncology.2008.06.005. Epub 2008 Aug 26.
Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. The present study was designed to examine the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC), and to investigate the possible role of CCR7/CCL21 interaction in neck lymph node metastasis of OSCC. By using immunohistochemistry, RT-PCR and Western Blot, expression of CCR7 was examined in 85 cases of oral squamous cell carcinoma, and Tca8113 and ACC cell lines. CCL21-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. In vitro adhesion assay was shown for banding of tumor cell lines to submandibular lymph nodes with or without anti-CCR7 antibody treatment. Immunohistochemical staining showed 65.9% (56/85) of positive CCR7 expression in OSCC tissues. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P=0.015) and was also associated with tumor size (P=0.014), and clinical stage (P=0.009). RT-PCR and Western Blot also confirmed positive CCR7 expression in oral squamous cell carcinoma and Tca8113 cell line, and negative CCR7 expression in normal oral mucosa and ACC cell line. CCL21 stimulation increased the ability of CCR7-positive Tca8113 cells passing through the Matrigel membrane. CCR7-positive Tca8113 cells also showed stronger adhesion to lymph nodes, which could be partly blocked by anti-CCR7 antibody incubation. These results indicated that the chemotactic CCR7/CCL21 interaction may be a possible mechanism for induction of directional lymph node metastasis by oral squamous cell carcinoma.
肿瘤细胞迁移和转移与白细胞迁移有许多相似之处，白细胞迁移受趋化因子及其受体的严格调控。本研究旨在检测趋化因子受体 CCR7 在口腔鳞状细胞癌（OSCC）中的表达，并探讨 CCR7/CCL21 相互作用在 OSCC 颈部淋巴结转移中的可能作用。通过免疫组织化学、RT-PCR 和 Western blot 检测了 85 例口腔鳞状细胞癌和 Tca8113 和 ACC 细胞系中 CCR7 的表达。在 Matrigel 包被的趋化室中检测 CCL21 介导的细胞迁移。体外黏附实验显示，肿瘤细胞系与颌下淋巴结的黏附带，或用抗 CCR7 抗体处理。免疫组织化学染色显示 65.9%（56/85）的 OSCC 组织中 CCR7 表达阳性。有淋巴结转移的患者 CCR7 表达明显高于无淋巴结转移的患者（P=0.015），且与肿瘤大小（P=0.014）和临床分期（P=0.009）相关。RT-PCR 和 Western blot 也证实了口腔鳞状细胞癌和 Tca8113 细胞系中 CCR7 的阳性表达，以及正常口腔黏膜和 ACC 细胞系中 CCR7 的阴性表达。CCL21 刺激增强了 CCR7 阳性 Tca8113 细胞穿过 Matrigel 膜的能力。CCR7 阳性 Tca8113 细胞对淋巴结的黏附性也更强，这可部分被抗 CCR7 抗体孵育阻断。这些结果表明，趋化 CCR7/CCL21 相互作用可能是口腔鳞状细胞癌诱导定向淋巴结转移的一种可能机制。
