Orexin 2 receptor as a potential target for immunotoxin and antibody-drug conjugate cancer therapy

Kishida,Masato; Ishige,Kazunori; Horibe,Tomohisa; Tada,Noriko; Koibuchi,Nobutaka; Shoda,Junichi; Kita,Kiyoshi; Kawakami,Koji

doi:10.3892/ol.2011.528

Orexin 2 receptor as a potential target for immunotoxin and antibody-drug conjugate cancer therapy

Authors:
- Masato Kishida
- Kazunori Ishige
- Tomohisa Horibe
- Noriko Tada
- Nobutaka Koibuchi
- Junichi Shoda
- Kiyoshi Kita
- Koji Kawakami
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Affiliations: Department of Biomedical Chemistry, Graduate school of Medicine, The University of Tokyo, Tokyo 113‑0033, Japan, Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto 606-8501, Japan, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto 606-8501, Japan, Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kamamoto 860-8556, Japan, Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Published online on: December 19, 2011 https://doi.org/10.3892/ol.2011.528
Pages: 525-529

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Abstract

Targeting tumor-specific receptors is a promising approach for cytotoxic agents. The orexin 2 receptor (OX2R) has reportedly been expressed in a few types of cancer, but not in normal, cells. This study aimed to explore and assess the expression levels of OX2R in a wide range of cancer cell lines and clinical samples to identify its localization. To analyze OX2R expression, we developed a polyclonal antibody specific to OX2R by immunizing two rabbits with a peptide cocktail. A total of 36 cancer cell lines were employed for reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, and 221 samples from various tissue arrays were used for the immunohistochemistry of OX2R expression. OX2R was identified in three cancerous cell lines, from the gallbladder, squamous cell carcinoma of the head and neck (SCCHN) and glioblastoma. With clinical samples of tissue arrays, 69/221 (31.2%) samples reacted positively with the OX2R antibody. We confirmed its presence on the cell membrane. In conclusion, OX2R was identified on several cancer cells as well as clinical samples. Further studies with larger numbers of clinical samples are required to confirm the statistical significance of the presence and relationships of OX2R with tumor histology. Results of the current study suggested that OX2R is a potent target for immunotoxin or antibody-drug conjugate (ADC) cancer therapy on OX2R-positive cancer cells.

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