Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells
Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells
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DOI：
10.1038/s41598-019-48764-3
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发表时间：
2019-08-28
影响因子：
4.6
通讯作者：
Beebe, David J.
中科院分区：
文献类型：
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作者：
Ayuso, Jose M.;Vitek, Ross;Beebe, David J.
EGFR通路在头颈部鳞状细胞癌(HNSCC)中起关键作用。针对EGFR的靶向治疗被用作HNSCCC的治疗方法。然而，患者的反应是异质性的，缺乏分子生物标记物来预测患者的反应。因此，直接在肿瘤细胞中评估药物反应的功能分析是一个有趣的选择。先前的研究表明，实验条件改变了在功能分析中观察到的药物反应。因此，本工作评价了培养环境对西妥昔单抗(EGFR单抗)和AZD8055(mTOR抑制剂)反应的影响。将HNSCC UM-SCC-1和UM-SCC-47细胞在2D单一培养条件下进行培养，并与肿瘤相关成纤维细胞(CAF)2D共培养、胶原水凝胶3D培养和肿瘤球体3D培养进行比较。结果表明，UM-SCC-1在不同培养环境下的药物反应发生明显变化，导致CAF共培养和3D球体的耐药性增加。相反，UM-SCC-47在不同培养条件下表现出更恒定的药物反应。总之，这项工作强调了调节对EGFR途径抑制反应的培养条件的重要性。
The EGFR pathway plays a critical role in head and neck squamous cell carcinoma (HNSCC). Targeted therapies against the EGFR are utilized as a treatment for HNSCCC. However, patient response is heterogeneous and molecular biomarkers are lacking to predict patient response. Therefore, functional assays where drug response is directly evaluated in tumor cells are an interesting alternative. Previous studies have shown that experimental conditions modify the drug response observed in functional assays. Thus, in this work the influence of the culture environment on response to Cetuximab (EGFR monoclonal antibody) and AZD8055 (mTOR inhibitor) was evaluated. HNSCC UM-SCC-1 and UM-SCC-47 cells were cultured in 2D monoculture and compared with: 2D co-culture with cancer-associated fibroblasts (CAF); 3D culture in collagen hydrogels; and 3D culture in tumor spheroids. The results showed UM-SCC-1 drug response significantly changed in the different culture environments; leading to an increase in drug resistance in the CAF co-culture and the 3D spheroids. Conversely, UM-SCC-47 exhibited a more constant drug response across culture conditions. In conclusion, this work highlights the importance of culture conditions that modulate response to EGFR pathway inhibition.