CCR7-CCL21 axis promotes the cervical lymph node metastasis of tongue squamous cell carcinoma by up-regulating MUC1.

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.