Department of Otorhinolaryngology, Head and Neck Surgery, Lund University, 221 85 Lund, Sweden.
J Cancer Res Clin Oncol. 2012 Mar;138(3):491-9. doi: 10.1007/s00432-011-1127-5. Epub 2011 Dec 23.
Predictive strategies for the treatment efficacy of cetuximab are currently not available for head and neck cancer. We investigated the correlation between the expression of epidermal growth factor receptor (EGFR) ligands and EGFR expression, and the growth inhibitory activity of cetuximab in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines.
The growth inhibiting effect of cetuximab was measured for eight HNSCC cell lines and correlated with the autocrine production of five EGFR ligands as measured by ELISA, and the mRNA expression of two ligands, as measured by quantitative RT-PCR. EGFR expression was assessed by western blot analysis.
There was a good correlation between the expression of four of the EGFR ligands (TGF-α, amphiregulin, epiregulin and epigen) and the growth inhibiting effect of cetuximab. TGF-α had the highest predictive potential but had to be combined with epigen for full prediction. EGFR expression also correlated with cetuximab sensitivity but less clearly.
The results indicate that the expression of several EGFR ligands has to be used to predict sensitivity to cetuximab in HNSCC. This has to be further evaluated in clinical samples.
目前尚无预测西妥昔单抗治疗头颈部癌症疗效的策略。我们研究了表皮生长因子受体（EGFR）配体的表达与 EGFR 表达之间的相关性，以及西妥昔单抗在一系列头颈部鳞状细胞癌（HNSCC）细胞系中的生长抑制活性。
用 ELISA 法测定 8 种 HNSCC 细胞系中五种 EGFR 配体的自分泌产生情况，并用定量 RT-PCR 法测定两种配体的 mRNA 表达情况，来测定西妥昔单抗的生长抑制作用，并与西妥昔单抗的生长抑制作用相关联。用 Western blot 分析 EGFR 表达。
四种 EGFR 配体（TGF-α、 Amphiregulin、Epiregulin 和 epigen）的表达与西妥昔单抗的生长抑制作用有很好的相关性。TGF-α 具有最高的预测潜能，但必须与 epigen 联合使用才能进行全面预测。EGFR 表达也与西妥昔单抗敏感性相关，但不太明确。
结果表明，几种 EGFR 配体的表达必须用于预测 HNSCC 对西妥昔单抗的敏感性。这需要在临床样本中进一步评估。
