Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Cell Signal. 2018 Jul;47:122-130. doi: 10.1016/j.cellsig.2018.04.001. Epub 2018 Apr 10.
Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway.
放射疗法是一种成熟的治疗方式，用于治疗许多癌症。然而，放射抗性仍然是成功治疗的严重障碍。放射抗性可导致一些患者在放射治疗后局部复发和远处转移。因此，许多研究试图确定有效的放射增敏剂。Eph 受体功能有助于肿瘤的发展，调节细胞-细胞黏附、侵袭、新生血管生成、肿瘤生长和转移。然而，EphA3 在放射抗性中的作用尚不清楚。在本研究中，我们建立了一个稳定的耐放射头颈癌细胞系（AMC HN3R 细胞系），通过 DNA 微阵列、实时 PCR 和 Western blot 发现 EphA3 在耐放射头颈癌细胞系中表达明显。此外，我们发现 EphA3 在放射治疗后的复发性喉癌标本中过表达。EphA3 介导耐放射头颈癌细胞系的肿瘤侵袭和迁移以及上皮间质转化相关蛋白表达。抑制 EphA3 可增强体外和体内 AMC HN3R 细胞系的放射敏感性。总之，我们的研究结果表明，EphA3 在耐放射头颈癌中过度表达，并通过调节上皮间质转化途径在头颈部癌症的放射抗性发展中起关键作用。
