Derivation of a new model of lung adenocarcinoma using canine lung cancer organoids for translational research in pulmonary medicine

Yomogi Shiota (Sato); Mohamed Elbadawy; Kazuhiko Suzuki; Ryouichi Tsunedomi; Hiroaki Nagano; Yusuke Ishihara; Haru Yamamoto; Daigo Azakami; Tsuyoshi Uchide; Ryuji Fukushima; Ryo Tanaka; Tomohiko Yoshida; Takuya Mori; Amira Abugomaa; Masahiro Kaneda; Hideyuki Yamawaki; Yuta Shinohara; Mohamed Aboubakr; Mohamed E. El-Asrag; Tatsuya Usui; Kazuaki Sasaki

Biomedicine & Pharmacotherapy (Sep 2023)

Derivation of a new model of lung adenocarcinoma using canine lung cancer organoids for translational research in pulmonary medicine

Yomogi Shiota (Sato),
Mohamed Elbadawy,
Kazuhiko Suzuki,
Ryouichi Tsunedomi,
Hiroaki Nagano,
Yusuke Ishihara,
Haru Yamamoto,
Daigo Azakami,
Tsuyoshi Uchide,
Ryuji Fukushima,
Ryo Tanaka,
Tomohiko Yoshida,
Takuya Mori,
Amira Abugomaa,
Masahiro Kaneda,
Hideyuki Yamawaki,
Yuta Shinohara,
Mohamed Aboubakr,
Mohamed E. El-Asrag,
Tatsuya Usui,
Kazuaki Sasaki

Affiliations

Yomogi Shiota (Sato): Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Mohamed Elbadawy: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, 13736, Moshtohor, Toukh, Elqaliobiya, Egypt; Corresponding author at: Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, 13736, Moshtohor, Toukh, Elqaliobiya, Egypt. Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan.
Kazuhiko Suzuki: Laboratory of Veterinary Toxicology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Ryouichi Tsunedomi: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1–1-1 Minami-Kogushi, Ube, Yamaguchi 755–8505, Japan
Hiroaki Nagano: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1–1-1 Minami-Kogushi, Ube, Yamaguchi 755–8505, Japan
Yusuke Ishihara: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Haru Yamamoto: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Daigo Azakami: Laboratory of Veterinary Clinical Oncology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Tsuyoshi Uchide: Laboratory of Veterinary Molecular Pathology and Therapeutics, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Ryuji Fukushima: Animal Medical Emergency Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 2–24-16 Nakamachi, Koganei, Tokyo 184–8588, Japan
Ryo Tanaka: Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Tomohiko Yoshida: Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Takuya Mori: Kinki Animal Medical Study Center, 3–15-27, Hishie, Osaka 578–0984, Japan
Amira Abugomaa: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan; Faculty of Veterinary Medicine, Mansoura University, 35516 Mansoura, Egypt
Masahiro Kaneda: Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan
Hideyuki Yamawaki: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, 35–1, Higashi 23 ban-cho, Towada, Aomori 034–8628, Japan
Yuta Shinohara: Pet Health & Food Division, Iskara Industry CO., LTD, 1–14-2, Nihonbashi, Chuo-ku, Tokyo 103–0027, Japan
Mohamed Aboubakr: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, 13736, Moshtohor, Toukh, Elqaliobiya, Egypt
Mohamed E. El-Asrag: Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
Tatsuya Usui: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan; Corresponding author.
Kazuaki Sasaki: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3–5-8 Saiwai-cho, Fuchu, Tokyo 183–8509, Japan

Journal volume & issue: Vol. 165
p. 115079

Abstract

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Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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