Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
Mol Cancer Res. 2012 Nov;10(11):1430-9. doi: 10.1158/1541-7786.MCR-12-0276. Epub 2012 Sep 21.
Interleukin-20 (IL-20) is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, little is known about the role of IL-20 in oral cancer. We explored the function of IL-20 in the tumor progression of oral cancer. IL-20 expression levels in tumorous and nontumorous oral tissue specimens from 40 patients with four different stages oral cancer were analyzed with immunohistochemistry (IHC) staining and quantitative real-time PCR (qRT-PCR). Expression of IL-20 and its receptor subunits was higher in clinical oral tumor tissue than in nontumorous oral tissue. The role of IL-20 was examined in two oral cancer cell lines (OC-3 and OEC-M1). In vitro, IL-20 promoted TNF-α, IL-1β, MCP-1, CCR4, and CXCR4 and increased proliferation, migration, reactive oxygen species (ROS) production, and colony formation of oral cancer cells via activated STAT3 and AKT/JNK/ERK signals. To evaluate the therapeutic potential of anti-IL-20 monoclonal antibody 7E for treating oral cancer, an ex vivo tumor growth model was used. In vivo, 7E reduced tumor growth and inflammation in oral cancer cells. In conclusion, IL-20 promoted oral tumor growth, migration, and tumor-associated inflammation. Therefore, IL-20 may be a novel target for treating oral cancer, and anti-IL-20 monoclonal antibody 7E may be a feasible therapeutic.
白细胞介素-20(IL-20)是一种促炎细胞因子,参与类风湿关节炎、动脉粥样硬化和骨质疏松症的发生。然而,关于 IL-20 在口腔癌中的作用知之甚少。我们探讨了 IL-20 在口腔癌肿瘤进展中的作用。通过免疫组织化学(IHC)染色和实时定量 PCR(qRT-PCR)分析了 40 例不同阶段口腔癌患者肿瘤和非肿瘤口腔组织标本中 IL-20 的表达水平。IL-20 和其受体亚基在临床口腔肿瘤组织中的表达高于非肿瘤口腔组织。在两种口腔癌细胞系(OC-3 和 OEC-M1)中检查了 IL-20 的作用。在体外,IL-20 通过激活 STAT3 和 AKT/JNK/ERK 信号促进 TNF-α、IL-1β、MCP-1、CCR4 和 CXCR4 的表达,增加口腔癌细胞的增殖、迁移、活性氧(ROS)产生和集落形成。为了评估抗 IL-20 单克隆抗体 7E 治疗口腔癌的治疗潜力,使用了离体肿瘤生长模型。在体内,7E 减少了口腔癌细胞的肿瘤生长和炎症。总之,IL-20 促进了口腔肿瘤的生长、迁移和肿瘤相关炎症。因此,IL-20 可能是治疗口腔癌的新靶点,抗 IL-20 单克隆抗体 7E 可能是一种可行的治疗方法。