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Abstract
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.

Author information

Kim SH1, Lee WH1, Kim SW2, Je HU3, Lee JC1, Chang HW4, Kim YM5, Kim K5, Kim SY6, Han MW7.
1
Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
2
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Department of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
4
Biomedical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
5
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
6
Department of otolaryngology, Asan medical center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: sykim2@amc.seoul.kr.
7
Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea. Electronic address: brightmoon@uuh.ulsan.kr.