Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Oral Diagnosis and Dent-maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1267-1272. doi: 10.1016/j.bbrc.2018.07.035. Epub 2018 Jul 13.
Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.
表皮生长因子受体 (EGFR) 的遗传扩增、过表达和信号转导增强在口腔鳞状细胞癌 (OSCC) 中经常发现，因此 EGFR 经常被治疗性抗体西妥昔单抗靶向分子治疗。我们评估了西妥昔单抗对控制 OSCC 细胞中 EGF 驱动的恶性特征的影响。EGF 刺激促进了 OSCC 细胞间充质特征的进展水平，西妥昔单抗可减弱但不完全抑制其作用。我们探讨了这种不完全抑制 OSCC 恶性特征的潜在机制。西妥昔单抗促进 OSCC 细胞分泌 EGFR-EVs，并且不能抑制 EGF 驱动的 EGFR-EVs 分泌。还发现西妥昔单抗与 OSCC 细胞分泌的 EGFR-EVs 一起被强烈分泌。因此，EGF 促进了 OSCC 细胞间质特征的水平和 EGFR-EVs 的分泌，这涉及西妥昔单抗的耐药性。
