Zhang Zongmeng, Du Jinlin, Xu Qihua, Li Yuyu, Zhou Sujin, Zhao Zhenggang, Mu Yunping, Zhao Allan Z, Cao Su-Mei, Li Fanghong
The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Cancers (Basel). 2022 Dec 5;14(23):6003. doi: 10.3390/cancers14236003.
NPC is a type of malignant tumor with a high risk of local invasion and early distant metastasis. Resistin is an inflammatory cytokine that is predominantly produced from the immunocytes in humans. Accumulating evidence has suggested a clinical association of circulating resistin with the risk of tumorigenesis and a relationship between blood resistin levels and the risk of cancer metastasis. In this study, we explored the blood levels and the role of resistin in NPC. High resistin levels in NPC patients were positively associated with lymph node metastasis, and resistin promoted the migration and invasion of NPC cells in vitro. These findings were also replicated in a mouse model of NPC tumor metastasis. We identified TLR4 as a functional receptor in mediating the pro-migratory effects of resistin in NPC cells. Furthermore, p38 MAPK and NF-κB were intracellular effectors that mediated resistin-induced EMT. Taken together, our results suggest that resistin promotes NPC metastasis by activating the TLR4/p38 MAPK/NF-κB signaling pathways.
鼻咽癌是一种具有局部侵袭和早期远处转移高风险的恶性肿瘤。抵抗素是一种主要由人类免疫细胞产生的炎性细胞因子。越来越多的证据表明循环抵抗素与肿瘤发生风险存在临床关联，且血液抵抗素水平与癌症转移风险之间存在关联。在本研究中，我们探讨了抵抗素在鼻咽癌中的血液水平及其作用。鼻咽癌患者的高抵抗素水平与淋巴结转移呈正相关，且抵抗素在体外促进了鼻咽癌细胞的迁移和侵袭。这些发现也在鼻咽癌肿瘤转移的小鼠模型中得到了验证。我们确定Toll样受体4（TLR4）是介导抵抗素对鼻咽癌细胞促迁移作用的功能性受体。此外，p38丝裂原活化蛋白激酶（p38 MAPK）和核因子κB（NF-κB）是介导抵抗素诱导的上皮-间质转化（EMT）的细胞内效应因子。综上所述，我们的结果表明抵抗素通过激活TLR4/p38 MAPK/NF-κB信号通路促进鼻咽癌转移。
