Taken together, our results demonstrate that CCR7 activation on thyroid carcinoma cells by CCL21 - a chemokine abundantly expressed in lymph nodes - favours tissue invasion and cell proliferation, and therefore may promote thyroid carcinoma growth and LNM.
In human breast carcinomas, mRNA expression of endothelins correlated with the level of CCR7 expression, both of which were associated with the presence of lymph node metastases.
High-intensity IHC staining for CXCR4 was associated with larger tumor size (P = .02), while PTCs exhibiting ETE, ALI, or lymph node metastasis showed higher-intensity IHC staining for CCR7 than those without (P = .01, .03, and .01, respectively).
Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively).
CCR7 and CXCR4 mRNAs were significantly higher in HNSCC tissues than in non-neoplastic tissues (p<0.05, respectively) and correlated with lymph node metastasis (p<0.05, respectively).
Immunohistochemical assay also showed that CCR7 and PKCα were highly expressed in SCCHN and correlated with each other, which was significantly related to lymph node metastasis and clinical stage.
Negative Dicer 1 protein and let-7a miRNA expression and positive CCR7 protein expression significantly correlated with lymph node metastasis, depth of invasion, high clinical TNM stage, and larger tumor size.
High CCR7 expression in gastric cancer cells was significantly associated with poor overall survival (OS) (P = 0.010) and lymph node metastasis (P = 0.009), and was an independent factor for worse OS (P = 0.023) by multivariate analysis.
These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients.
By immunohistolochemistry, high expressions of CCR7, Slug and N-cadherin were seen in 60, 65, and 76.67 % of tumors, respectively, and significantly associated with lymph node metastases as well as clinical pathological stage.
Our findings show that the molecular cues secreted by TALs alone or in combination with CCR7 may emerge as future therapeutic targets for lymph node metastasis in breast cancer patients.
The immunohistochemistry results also showed that the phosphorylation of STAT3 was correlated with CCR7 expression in SCCHN, and CCR7 and STAT3 phosphorylation were all associated with lymph node metastasis.
The pooled relative risks indicated CCR7 expression was significantly associated with deeper tumor invasion [0.61, 95 % confidence interval (CI) 0.45-0.84, p = 0.003], advanced stage (0.47, 95 % CI 0.32-0.69, p < 0.001), vascular invasion (2.12, 95 % CI 1.20-3.73, p = 0.009), lymph node metastasis (2.00, 95 % CI 1.48-2.70, p < 0.001), and lymphatic invasion (1.98, 95 % CI 1.43-2.72, p < 0.001) but not with age, tumor size, and histological type.