Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma
Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma
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DOI：
10.1002/path.2935
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发表时间：
2011-09-01
影响因子：
7.3
通讯作者：
Ando, Yukio
中科院分区：
文献类型：
--
作者：
Shinriki, Satoru;Jono, Hirofumi;Ando, Yukio
淋巴结转移与口腔鳞状细胞癌（OSCC）患者对常规治疗的耐药性和较差的生存率相关。虽然众所周知淋巴管生成与各种癌症的淋巴结转移有关，但OSCC中淋巴管生成的确切机制在很大程度上尚不清楚。IL-6是一种强效的促炎细胞因子，已被证明在包括OSCC在内的多种癌症中发挥积极作用。本研究旨在探讨IL-6信号在淋巴转移中的作用，并评估tocilizumab（一种人源化抗人IL-6受体抗体）作为OSCC抗淋巴管生成药物的疗效。本研究证实，通过免疫组织化学分析和实时定量RT-PCR检测，OSCC组织中IL-6蛋白和VEGF-C mRNA的表达水平与OSCC患者淋巴结转移有显著相关性。体外研究表明，IL-6通过磷酸肌苷3-激酶- akt通路调节人OSCC细胞系SAS细胞中VEGF-C mRNA的表达。此外，托珠单抗治疗导致SAS异种移植物中VEGF-C mRNA表达和oscc相关淋巴管生成显著降低。总之，这些数据表明tocilizumab的作用正如预期的那样：它通过减少肿瘤淋巴管生成来抑制OSCC的淋巴结转移。版权所有(C) 2011英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL-6, a potent pro-inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC. This study aimed to investigate the involvement of IL-6 signalling in lymphatic metastasis and to evaluate the efficacy of tocilizumab, a humanized anti-human IL-6 receptor antibody, as an anti-lymphangiogenic agent for OSCC. This investigation confirmed that levels of expression of IL-6 protein and VEGF-C mRNA in OSCC tissues were significantly correlated with lymph node metastasis in patients with OSCC, as assessed by immunohistochemical analysis and real-time quantitative RT-PCR. In vitro studies showed that IL-6 regulated VEGF-C mRNA expression in a human OSCC cell line, SAS cells, through the phosphoinositide 3-kinase-Akt pathway. In addition, treatment with tocilizumab led to markedly reduced VEGF-C mRNA expression and OSCC-related lymphangiogenesis in SAS xenografts. Together, these data suggest that tocilizumab acted as expected: it inhibited lymph node metastasis in OSCC by reducing tumour lymphangiogenesis. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.