The serum biomarker chemerin promotes tumorigenesis and metastasis in oral squamous cell carcinoma
The serum biomarker chemerin promotes tumorigenesis and metastasis in oral squamous cell carcinoma
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血清生物标志物凯莫瑞促进口腔鳞状细胞癌的肿瘤发生和转移
DOI：
10.1042/cs20181023
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发表时间：
2019-03-15
期刊：
影响因子：
6
通讯作者：
Wang, Anxun
中科院分区：
文献类型：
--
作者：
Lu, Zhiyuan;Liang, Jianfeng;Wang, Anxun
由视黄酸受体应答者2（RARRES 2）编码的Chemerin已被发现与恶性肿瘤相关，但其在口腔鳞状细胞癌（OSCC）发展中的作用在很大程度上未被探索。在本研究中，口腔鳞癌患者血清中chemerin水平明显高于健康人，肿瘤切除后chemerin水平显著降低。此外，高chemerin水平与晚期肿瘤分期和淋巴结转移呈正相关。Chemerin和Chemerin受体23（ChemR 23）的表达水平与OSCC细胞的迁移和侵袭能力呈正相关。重组chemerin（R-chemerin）以浓度依赖的方式增强OSCC细胞的体外迁移、侵袭和增殖，靶向RARRES 2的短发夹RNA（shRNAs）在体内外均能降低chemerin的表达，抑制OSCC细胞的转移和增殖。此外，R-chemerin激活锰超氧化物歧化酶（SOD 2）并增加细胞内过氧化氢（H2 O2）的量，导致E-cadherin表达显著降低，磷酸化ERK 1/2（p-ERK 1/2），Slug，Vimentin和N-cadherin表达显著增加，但靶向RARRES 2的shRNA逆转了这些作用。此外，敲低ChemR 23与小干扰RNA（siRNA）显着抑制chemerin诱导的OSCC细胞迁移/侵袭和SOD 2活性。我们的研究结果表明，chemerin是一种新的生物标志物的口腔鳞癌。Chemerin/ChemR 23可促进口腔鳞癌的发生和转移，有望成为口腔鳞癌治疗的新靶点。
Chemerin, which is encoded by retinoic acid receptor responder 2 (RARRES2), has been found to be related to malignant tumours, but its role in the development of oral squamous cell carcinoma (OSCC) is largely unexplored. In the present study, a higher serum level of chemerin was evident in patients with OSCC than in healthy individuals, and this high level of chemerin significantly decreased after tumour resection. In addition, high chemerin levels were positively associated with advanced tumour stage and lymph node metastasis. The expression levels of chemerin and Chemerin Receptor 23 (ChemR23) were positively correlated with the migration and invasion of OSCC cell lines. Recombinant chemerin (R-chemerin) enhanced the in vitro migration, invasion and proliferation of OSCC cells in a concentration-dependent manner, and short hairpin RNAs (shRNAs) targeting RARRES2 decreased chemerin expression and inhibited OSCC cell metastasis and proliferation both in vitro and in vivo. Additionally, R-chemerin activated manganese superoxide dismutase (SOD2) and increased the amount of intracellular hydrogen peroxide (H2O2), leading to a significant decrease in E-cadherin expression and dramatic increase in the expression of phosphorylated ERK1/2 (p-ERK1/2), Slug, Vimentin and N-cadherin, but shRNAs targeting RARRES2 reversed these effects. Moreover, knockdown of ChemR23 with small interfering RNAs (siRNA) significantly inhibited chemerin-induced OSCC cell migration/invasion and SOD2 activity. Our results revealed that chemerin is a novel biomarker for OSCC. Chemerin/ChemR23 promotes tumorigenesis and metastasis in OSCC and may be a new therapeutic target for OSCC.