Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition.
Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition.
复制标题
口腔鳞状细胞癌中表皮生长因子受体表达的丧失与侵袭性和上皮间质转化有关。
DOI：
10.3892/ol.2015.3833
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发表时间：
2016-01
期刊：
影响因子：
2.9
通讯作者：
Kawashiri S
中科院分区：
文献类型：
--
作者：
Kimura I;Kitahara H;Ooi K;Kato K;Noguchi N;Yoshizawa K;Nakamura H;Kawashiri S
抑制表皮生长因子受体（EGFR）信号转导已成为治疗口腔鳞状细胞癌（OSCC）的新策略。EGFR靶向抑制剂西妥昔单抗是目前唯一获批的用于治疗口腔鳞癌的靶向治疗药物。EGFR状态可能影响患者对西妥昔单抗治疗的应答。在本研究中，通过对EGFR免疫标记物的分析，发现58.3%的研究病例的EGFR表达阳性，而且，侵袭性与EGFR表达呈负相关。EGFR的表达水平进行了定量，EGFR表达和西妥昔单抗的敏感性之间的相关性进行了研究，使用三个不同等级的浸润性人口腔鳞癌线。EGFR在高级别浸润细胞中的表达较低级别浸润细胞明显下调。不同浓度的西妥昔单抗对高级别浸润细胞无明显的抗增殖作用。EMT相关基因N-cadherin、vimentin和Snail在高级别浸润细胞中表达上调。低度浸润细胞具有典型上皮细胞的特征，表达E-cadherin，不表达N-cadherin、vimentin和Snail。转化生长因子-β诱导低度侵袭性细胞经历上皮-间充质转化（EMT）相关的基因开关，这导致低水平的EGFR表达。本研究的结果表明，表皮生长因子受体表达的损失在口腔鳞癌与EMT，并可能有功能方面的影响，肿瘤的侵袭性和耐药性西妥昔单抗治疗。
Inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as a novel therapeutic strategy for the treatment of oral squamous cell carcinoma (OSCC). The EGFR-directed inhibitor cetuximab is currently the only approved targeted therapy for the treatment of OSCC. EGFR status may affect the patient response to cetuximab treatment. In the present study, via analysis of the immunomarker for EGFR, it was revealed that 58.3% of the total cases investigated stained positively for EGFR expression, and furthermore, that invasiveness was inversely correlated with EGFR expression. Expression levels of EGFR were quantified, and the correlation between EGFR expression and cetuximab sensitivity was investigated using three varying grades of invasive human OSCC line. EGFR expression in high-grade invasive cells was significantly downregulated compared with that of low-grade invasive cells. There was no significant antiproliferative effect in the high-grade invasive cells treated with various concentrations of cetuximab. The EMT-associated genes, N-cadherin, vimentin and Snail, were upregulated in the high-grade invasive cells. The low-grade invasive cells exhibited characteristics of typical epithelial cells, including the expression of E-cadherin and absence of the expression of N-cadherin, vimentin and Snail. Transforming growth factor-β induced low-grade invasive cells to undergo an epithelial-mesenchymal transition (EMT)-associated gene switch, which resulted in low levels of EGFR expression. The results of the present study suggested that loss of EGFR expression in OSCC was associated with EMT, and may have functional implications with regard to tumor invasiveness and the resistance to cetuximab treatment.