Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden.
Department of Clinical Pathology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
J Oral Pathol Med. 2017 Oct;46(9):717-724. doi: 10.1111/jop.12545. Epub 2017 Jan 28.
The aims of this study were to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC) cell lines in an in vivo xenograft model and to identify treatment-induced changes in the epidermal growth factor receptor (EGFR) signaling pathway that could be used as markers for cetuximab treatment response.
The in vitro and in vivo cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UT-SCC-45, was assessed using a crystal violet assay and xenografts in nude mice, respectively. The expression of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki-67 was investigated by immunohistochemistry. To verify these results, the in vitro expression of EGFR and pEGFR was analyzed with ELISA in a panel of 10 HNSCC cell lines.
A close correlation was found between in vitro and in vivo cetuximab sensitivity data in the two investigated HNSCC cell lines. In treatment sensitive UT-SCC-14 xenografts, there was a decrease in EGFR, pEGFR, and pSrc upon cetuximab treatment. Interestingly, in insensitive UT-SCC-45 xenografts, an increased expression of these three proteins was found. The change in EGFR and pEGFR expression in vivo was confirmed in cetuximab-sensitive and cetuximab-insensitive HNSCC cell lines using ELISA.
High sensitivity to cetuximab was strongly associated with a treatment-induced reduction in pEGFR both in vivo and in vitro in a panel of HNSCC cell lines, suggesting that EGFR and pEGFR dynamics could be used as a predictive biomarker for cetuximab treatment response.
本研究的目的是验证头颈部鳞状细胞癌（HNSCC）细胞系在体内异种移植模型中的体外药物敏感性检测，并确定治疗诱导的表皮生长因子受体（EGFR）信号通路变化，可作为西妥昔单抗治疗反应的标志物。
采用结晶紫法和裸鼠异种移植分别评估了两种 HNSCC 细胞系 UT-SCC-14 和 UT-SCC-45 的体外和体内西妥昔单抗敏感性。通过免疫组织化学法检测 EGFR、磷酸化 EGFR（pEGFR）、磷酸化Src（pSrc）和 Ki-67 的表达。为了验证这些结果，使用 ELISA 分析了 10 种 HNSCC 细胞系中 EGFR 和 pEGFR 的体外表达。
在两种研究的 HNSCC 细胞系中，发现体外和体内西妥昔单抗敏感性数据之间存在密切相关性。在治疗敏感的 UT-SCC-14 异种移植中，西妥昔单抗治疗后 EGFR、pEGFR 和 pSrc 表达下降。有趣的是，在不敏感的 UT-SCC-45 异种移植中，发现这三种蛋白的表达增加。使用 ELISA 在西妥昔单抗敏感和不敏感的 HNSCC 细胞系中证实了体内 EGFR 和 pEGFR 表达的变化。
在一组 HNSCC 细胞系中，高西妥昔单抗敏感性与体内和体外 pEGFR 治疗诱导降低强烈相关，表明 EGFR 和 pEGFR 动力学可作为西妥昔单抗治疗反应的预测生物标志物。
