The translation elongation factor eEF2 is a novel tumor‑associated antigen overexpressed in various types of cancers

Oji,Yusuke; Tatsumi,Naoya; Fukuda,Mari; Nakatsuka,Shin-Ichi; Aoyagi,Sayaka; Hirata,Erika; Nanchi,Isamu; Fujiki,Fumihiro; Nakajima,Hiroko; Yamamoto,Yumiko; Shibata,Syohei; Nakamura,Michiyo; Hasegawa,Kana; Takagi,Sayaka; Fukuda,Ikuyo; Hoshikawa,Tomoko; Murakami,Yui; Mori,Masahide; Inoue,Masayoshi; Naka,Tetsuji; Tomonaga,Takeshi; Shimizu,Yoshifumi; Nakagawa,Masashi; Hasegawa,Junichi; Nezu,Riichiro; Inohara,Hidenori; Izumoto,Shuichi; Nonomura,Norio; Yoshimine,Toshiki; Okumura,Meinoshin; Morii,Eiichi; Maeda,Hajime; Nishida,Sumiyuki; Hosen,Naoki; Tsuboi,Akihiro; Oka,Yoshihiro; Sugiyama,Haruo

doi:10.3892/ijo.2014.2318

The translation elongation factor eEF2 is a novel tumor‑associated antigen overexpressed in various types of cancers

Authors:
- Yusuke Oji
- Naoya Tatsumi
- Mari Fukuda
- Shin-Ichi Nakatsuka
- Sayaka Aoyagi
- Erika Hirata
- Isamu Nanchi
- Fumihiro Fujiki
- Hiroko Nakajima
- Yumiko Yamamoto
- Syohei Shibata
- Michiyo Nakamura
- Kana Hasegawa
- Sayaka Takagi
- Ikuyo Fukuda
- Tomoko Hoshikawa
- Yui Murakami
- Masahide Mori
- Masayoshi Inoue
- Tetsuji Naka
- Takeshi Tomonaga
- Yoshifumi Shimizu
- Masashi Nakagawa
- Junichi Hasegawa
- Riichiro Nezu
- Hidenori Inohara
- Shuichi Izumoto
- Norio Nonomura
- Toshiki Yoshimine
- Meinoshin Okumura
- Eiichi Morii
- Hajime Maeda
- Sumiyuki Nishida
- Naoki Hosen
- Akihiro Tsuboi
- Yoshihiro Oka
- Haruo Sugiyama
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Affiliations: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Pathology, Kansai Rosai Hospital, Hyogo, Japan, Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Thoracic Oncology, Toneyama National Hospital, Osaka, Japan, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Respiratory Medicine and Allergy, Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan, Laboratory of Proteome Research, National Institute of Biomedical Innovation, Osaka, Japan, Department of Internal Medicine, Takarazuka City Hospital, Hyogo, Japan, Department of Internal Medicine, Nissay Hospital, Osaka, Japan, Department of Surgery, Osaka Rosai Hospital, Osaka, Japan, Department of Otolaryngology and Sensory Organ Surgery, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan, Department of General Thoracic Surgery, Toneyama National Hospital, Osaka, Japan, Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Biomedical Informatics, Osaka University Graduate School of Medicine, Osaka, Japan
Published online on: March 4, 2014 https://doi.org/10.3892/ijo.2014.2318
Pages: 1461-1469
Copyright: © Oji et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.

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