Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, People's Republic of China.
J Cell Mol Med. 2019 Apr;23(4):2689-2701. doi: 10.1111/jcmm.14168. Epub 2019 Feb 15.
Metastasis is one of the primary causes for high mortality in patients with squamous cell carcinoma of the head and neck (SCCHN). Our previous study showed that chemokine (C-C motif) ligand 18 (CCL18), derived from tumour-associated macrophages (TAMs), regulates SCCHN metastasis by promoting epithelial-mesenchymal transition (EMT) and preserving stemness. However, the underlying mechanism needs to be further investigation. Interestingly, metadherin (MTDH) expression was induced when SCCHN cells were stimulated with recombinant CCL18 protein in this study. Suppressing MTDH expression reversed CCL18-induced migration, invasion and EMT in SCCHN cells. Furthermore, the NF-κB signalling pathway was involved in the MTDH knock-down cells with CCL18 stimulation. We performed ELISA to evaluate the CCL18 levels in the serums of 132 treatment-naive SCCHN patients, 25 patients with precancerous lesion and 32 healthy donors. Our results demonstrated that serum CCL18 levels were significantly higher in SCCHN patients than patients with precancerous lesion and healthy individuals. CCL18 levels were found to be significantly correlated with tumour classification, clinical stage, lymph node metastasis and histological grade in SCCHN patients. Thus, our findings suggest that CCL18 may serve as a potential biomarker for diagnosis of SCCHN and promote SCCHN invasion, migration and EMT by MTDH-NF-κB signalling pathway.
转移是头颈部鳞状细胞癌 (SCCHN) 患者高死亡率的主要原因之一。我们之前的研究表明，肿瘤相关巨噬细胞 (TAMs) 来源的趋化因子 (C-C 基序) 配体 18 (CCL18) 通过促进上皮间质转化 (EMT) 和维持干细胞特性来调节 SCCHN 转移。然而，其潜在机制仍需进一步研究。有趣的是，在这项研究中，当 SCCHN 细胞受到重组 CCL18 蛋白刺激时，会诱导 metadherin (MTDH) 表达。抑制 MTDH 表达可逆转 CCL18 诱导的 SCCHN 细胞迁移、侵袭和 EMT。此外，NF-κB 信号通路参与了 CCL18 刺激下 MTDH 敲低细胞的作用。我们通过 ELISA 评估了 132 例未经治疗的 SCCHN 患者、25 例癌前病变患者和 32 例健康供体血清中的 CCL18 水平。结果表明，SCCHN 患者血清 CCL18 水平明显高于癌前病变患者和健康个体。在 SCCHN 患者中，CCL18 水平与肿瘤分类、临床分期、淋巴结转移和组织学分级显著相关。因此，我们的研究结果表明，CCL18 可能作为 SCCHN 的潜在诊断生物标志物，通过 MTDH-NF-κB 信号通路促进 SCCHN 的侵袭、迁移和 EMT。
