Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells
Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells
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DOI：
10.1111/jop.12310
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Roberg, Karin
中科院分区：
文献类型：
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作者：
Ansell, Anna;Jedlinski, Adam;Roberg, Karin
背景技术背景：头颈部鳞状细胞癌通常与异常的表皮生长因子受体（EGFR）信号传导相关，其有助于肿瘤生长。在此，我们在三种舌癌细胞系中研究了EGFR配体在增殖和EGFR靶向治疗西妥昔单抗敏感性方面的功能重要性。表皮生长因子（EGF），双调蛋白（AR），和表皮调节蛋白（epiregulin，EPR）对肿瘤细胞增殖和西妥昔单抗反应的影响通过加入重组人（rh）蛋白或通过siRNA-介导的内源性配体产生的下调。EGFR的表达，激活和细胞分布进行了评估，通过Western印迹分析和免疫细胞化学。结果：EGF下调抑制所有调查的肿瘤细胞系的增殖，而EGFR过度表达和EGFR非过度表达细胞系之间的反应，以增加EGF的水平不同。此外，肿瘤细胞一致显示增加西妥昔单抗耐药性后，加入rhEGF，而EGF沉默与改善西妥昔单抗反应。关于AR和EPR的数据是inconclusions.CONCLUSIONS：我们的数据表明，EGF的量是决定肿瘤细胞增殖率和西妥昔单抗治疗舌癌的反应。因此，EGF是西妥昔单抗不良反应的潜在预测生物标志物和可能的治疗靶点。
BACKGROUND: Head and neck squamous cell carcinoma is frequently associated with aberrant epidermal growth factor receptor (EGFR) signaling, which contributes to tumor growth. Here, the functional importance of EGFR ligands in relation to proliferation and sensitivity to the EGFR-targeted therapy cetuximab was investigated in three tongue cancer cell lines.METHODS: The influence of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumor cell proliferation and cetuximab response was evaluated by the addition of recombinant human (rh) proteins or by siRNA-mediated downregulation of the endogenous ligand production. The expression, activation and cellular distribution of EGFR were assessed by Western blot analysis and immunocytochemistry.RESULTS: EGF downregulation suppressed the proliferation of all investigated tumor cell lines, whereas the response to an increased level of EGF differed between EGFR-overexpressing and EGFR-non-overexpressing cell lines. Furthermore, tumor cells consistently displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing was associated with an improved cetuximab response. The data regarding AR and EPR were inconclusive.CONCLUSIONS: Our data suggest that the amount of EGF is a determinant of the tumor cell proliferation rate and the response to cetuximab treatment in tongue cancer. Thus, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.