CCR7-CCL21 轴通过上调 MUC1 促进舌鳞癌颈部淋巴结转移。
CCR7-CCL21 axis promotes the cervical lymph node metastasis of tongue squamous cell carcinoma by up-regulating MUC1.
机构信息
Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, The Affiliated Stomatological Hospital of Nankai University, Tianjin, 300041, China; Department of Oral and Maxillofacial Surgery, Tianjin Stomatological Hospital, The Affiliated Stomatological Hospital of Nankai University, Tianjin, 300041, China; Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin Haihe Hospital, Tianjin, 300350, China.
Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, The Affiliated Stomatological Hospital of Nankai University, Tianjin, 300041, China.
出版信息
J Craniomaxillofac Surg. 2021 Jul;49(7):562-569. doi: 10.1016/j.jcms.2021.02.027. Epub 2021 Apr 20.
This study aims at investigating the potential role of MUC1 in CCR7-CCL21 axis-induced metastasis of tongue squamous cell carcinoma (TSCC). TSCC patients were selected for epidemiologic trends. The expression of CCR7 and MUC1 was detected via immunohistochemistry. SCC15 and CAL27 cells were induced by CCL21 and specific antibody to CCR7. Gene and protein expression was detected using qRT-PCR and western blotting. Migration and invasion capacities of TSCC cells were determined using wound healing and Transwell invasion assays. The male:female ratio of 78 patients was 1.6:1. Metastasis rate of cervical lymph nodes (CLNs) was 42.3%. CLN metastasis significantly correlated with T staging (P = 0.026), clinical staging (P = 0.024), and depth of invasion (DOI, P = 0.001). DOI significantly influenced CLN metastasis (P = 0.033, OR = 10.919) of TSCC, as did CCR7 (P = 0.041) and MUC1 (P = 0.026). The consistency of CCR7 and MUC1 expression was fairly good (Kappa = 0.683, P < 0.001). Reduced survival was significantly associated with higher expression of CCR7 (P = 0.039) and MUC1 (P = 0.030). CCL21 up-regulated MUC1 in SCC15 cells, which was inhibited when CCR7 was blocked. MUC1 positively correlated with TSCC cell migration and invasion. CCR7-CCL21 axis might promote CLN metastasis of TSCC by up-regulating MUC1. CCR7 and MUC1 show promise as potential biomarkers for TSCC treatment.
本研究旨在探讨 MUC1 在 CCR7-CCL21 轴诱导舌鳞状细胞癌（TSCC）转移中的潜在作用。选择 TSCC 患者进行流行病学趋势分析。采用免疫组织化学法检测 CCR7 和 MUC1 的表达。用 CCL21 和 CCR7 的特异性抗体诱导 SCC15 和 CAL27 细胞。采用 qRT-PCR 和 Western blot 检测基因和蛋白表达。采用划痕愈合和 Transwell 侵袭实验检测 TSCC 细胞的迁移和侵袭能力。78 例患者中男女性别比为 1.6:1。颈淋巴结（CLN）转移率为 42.3%。CLN 转移与 T 分期（P=0.026）、临床分期（P=0.024）和浸润深度（DOI，P=0.001）显著相关。DOI 显著影响 TSCC 的 CLN 转移（P=0.033，OR=10.919），CCR7（P=0.041）和 MUC1（P=0.026）也是如此。CCR7 和 MUC1 表达的一致性相当好（Kappa=0.683，P<0.001）。较高的 CCR7（P=0.039）和 MUC1（P=0.030）表达与生存率降低显著相关。CCL21 上调 SCC15 细胞中的 MUC1，当阻断 CCR7 时则受到抑制。MUC1 与 TSCC 细胞迁移和侵袭呈正相关。CCR7-CCL21 轴可能通过上调 MUC1 促进 TSCC 的 CLN 转移。CCR7 和 MUC1 有望成为 TSCC 治疗的潜在生物标志物。
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