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Abstract：
Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignancies. Advanced stages of the disease are associated with poor survival, highlighting a need for new treatment modalities. We previously showed that the proinflammatory cytokine interleukin-18 (IL-18) has a tumor suppressive role in OSCC. Here, we investigated the effects of IL-18 on proliferation, migration, and invasion of OSCC cells ex vivo and in vitro, and in nude mouse xenografts. We report that expression of tankyrase 2 (TNKS2), β-catenin, and N-cadherin was higher in tumor cells than in normal mucosae, whereas the expression of IL-18 and E-cadherin was higher in normal than in tumor tissues. Elevated expression of IL-18 (P < 0.01) and E-cadherin (P = 0.034) was associated with tumor differentiation, whereas expression of TNKS2 (P < 0.01), β-catenin (P = 0.012), and N-cadherin (P < 0.01) was associated with tumor de-differentiation. Furthermore, compared with the vector control, IL-18 overexpression promoted tumor cell migration and invasion (P < 0.01), but inhibited growth of tumor cell xenografts (P < 0.05). At the protein level, expression levels of IL-18 (P < 0.01), TNKS2 (P = 0.045), β-catenin (P = 0.028), and N-cadherin (P = 0.068) were upregulated in tumor cells after IL-18 overexpression compared with those of the vector control mice, whereas expression levels of E-cadherin (P = 0.045) were decreased. In conclusion, our data suggest that IL-18 overexpression induces oral SCC cell invasion and metastasis by promoting the tumor cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.
摘要：
口腔鳞状细胞癌（OSCC）是最常见的头颈部恶性肿瘤之一。这种疾病的晚期阶段与低生存率有关，强调需要新的治疗方式。我们先前表明，促炎细胞因子白介素18（IL-18）在OSCC中具有肿瘤抑制作用。这里,我们研究了IL-18对增殖的影响，迁移,和OSCC细胞的体外和离体侵袭，和裸鼠异种移植物。我们报道了tankyrase2(TNKS2)的表达，β-连环蛋白，肿瘤细胞中的N-钙粘蛋白高于正常粘膜，而IL-18和E-cadherin在正常组织中的表达高于肿瘤组织。IL-18(P<0.01)和E-cadherin(P=0.034)的表达与肿瘤分化有关,而TNKS2的表达（P<0.01），β-连环蛋白（P=0.012），N-cadherin与肿瘤的去分化有关(P<0.01)。此外，与矢量控制相比，IL-18过表达促进肿瘤细胞迁移和侵袭(P<0.01),但抑制肿瘤细胞移植瘤的生长(P<0.05)。在蛋白质水平，IL-18的表达水平（P<0.01），TNKS2(P=0.045),β-连环蛋白（P=0.028），IL-18过表达后，与载体对照小鼠相比，肿瘤细胞中N-cadherin（P=0.068）上调，而E-cadherin的表达水平下降(P=0.045)。总之,我们的数据提示IL-18过表达通过Wnt/β-catenin信号通路促进肿瘤细胞上皮-间质转化,从而诱导口腔SCC细胞侵袭和转移.
