Significance of the TGF-β1/IL-6 axis in oral cancer.
Significance of the TGF-β1/IL-6 axis in oral cancer.
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DOI：
10.1042/cs20110434
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发表时间：
2012-05-01
期刊：
影响因子：
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通讯作者：
Chen WC
中科院分区：
文献类型：
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作者：
Chen MF;Wang WH;Lin PY;Lee KD;Chen WC
本研究的目的是探索特定的分子标记，从而为口腔癌创新治疗的识别提供新的见解。转化生长因子-β-1(Transform Growth For-β-1，TGF1)在口腔癌中的作用及其对预后的预测作用已被证实。选取人口腔癌细胞系SCC4和SCC25进行细胞实验。在体外研究了肿瘤侵袭性、治疗反应和相关信号通路的变化。此外，将125例口腔癌组织构建成组织芯片进行免疫组织化学分析，以探讨转化生长因子-β-1的表达与临床预后的关系。利用体外实验，我们的结果显示，激活的转化生长因子-β1信号导致更具侵袭性的肿瘤生长，增强上皮-间充质转化和更多的抗药性。IL-6(IL-6)信号的激活可能是转化生长因子-β1治疗口腔癌的机制之一。在临床资料方面，口腔癌组织中转化生长因子-β-1免疫反应阳性率显著高于非恶性上皮组织，且与IL-6染色呈正相关。此外，在病理III-IV期口腔癌患者中，转化生长因子-β-1的表达与淋巴结转移、疾病复发和较短的生存期显著相关。结论：转化生长因子-β-1/IL-6轴对口腔癌的预后有预测作用，靶向转化生长因子-β-1可能是一种有前途的治疗策略。
The aim of the present study was to explore specific molecular markers that could lead to new insights into the identification of innovative treatments in oral cancer. The role of TGF-β1 (transforming growth factor-β1) and its predictive power in the prognosis of oral cancer has been identified. Human oral cancer cell lines, including SCC4 and SCC25, were selected for cellular experiments. Changes in tumour aggressiveness, responses to treatment and the signalling pathway responsible were investigated in vitro. Furthermore, 125 oral cancer tissue specimens were constructed into tissue microarray blocks for immunohistochemical analysis to correlate the expression of TGF-β1 with clinical outcome. Using in vitro experiments, our results revealed that activated TGF-β1 signalling resulted in more aggressive tumour growth, augmented the epithelial–mesenchymal transition and more resistance to treatment. Activated IL-6 (interleukin-6) signalling could be the mechanism underlying the effects of TGF-β1 on oral cancer. Regarding clinical data, the incidence of TGF-β1 immunoreactivity in oral cancer specimens was significantly higher than in non-malignant epithelium and positively linked to IL-6 staining. Furthermore, expression of TGF-β1 was significantly correlated with the risk of lymph node involvement, disease recurrence and shorter survival in patients with pathological stage III–IV oral cancer. In conclusion, the TGF-β1/IL-6 axis had predictive power in the prognosis of oral cancer, and targeting TGF-β1 could represent a promising treatment strategy.