Establishment of an experimental model of canine malignant mesothelioma organoid culture using a three-dimensional culture method

被引:11
作者
Sato, Yomogi [1 ]
Elbadawy, Mohamed [1 ,2 ]
Suzuki, Kazuhiko [3 ]
Tsunedomi, Ryouichi [4 ]
Nagano, Hiroaki [4 ]
Ishihara, Yusuke [1 ]
Yamamoto, Haru [1 ]
Azakami, Daigo [5 ]
Uchide, Tsuyoshi [6 ]
Nabeta, Rina [6 ]
Fukushima, Ryuji [7 ]
Abugomaa, Amira [1 ,8 ]
Kaneda, Masahiro [9 ]
Yamawaki, Hideyuki [10 ]
Shinohara, Yuta
Usui, Tatsuya [1 ]
Sasaki, Kazuaki [1 ]
机构
[1] Tokyo Univ Agr & Technol, Fac Agr, Dept Vet Med, Lab Vet Pharmacol, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan
[2] Benha Univ, Fac Vet Med, Dept Pharmacol, Toukh 13736, Elqaliobiya, Egypt
[3] Tokyo Univ Agr & Technol, Fac Agr, Dept Vet Med, Lab Vet Toxicol, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan
[4] Yamaguchi Univ, Dept Gastroenterol Breast & Endocrine Surg, Grad Sch Med, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan
[5] Tokyo Univ Agr & Technol, Fac Agr, Lab Vet Clin Oncol, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan
[6] Tokyo Univ Agr & Technol, Fac Agr, Lab Vet Mol Pathol & Therapeut, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan
[7] Tokyo Univ Agr & Technol, Fac Agr, Anim Med Emergency Ctr, 2-24-16 Nakamachi, Koganei, Tokyo 1848588, Japan
[8] Mansoura Univ, Fac Vet Med, Mansoura 35516, Egypt
[9] Tokyo Univ Agr & Technol, Fac Agr, Dept Vet Med, Lab Vet Anat, 3-5-8 Saiwai Cho, Fuchu, Tokyo 1838509, Japan
[10] Kitasato Univ, Sch Vet Med, Lab Vet Pharmacol, 35-1,Higashi 23 Ban Cho, Towada, Aomori 0348628, Japan
关键词
Pleural mesothelioma; Dogs; Organoids; RNA-seq; Cell adhesion; EMT; EPITHELIAL-MESENCHYMAL TRANSITION; PLEURAL MESOTHELIOMA; CELL-LINES; EXPRESSION; DOG; ADHESION; HEALTH; GROWTH; TUMORS;
D O I
10.1016/j.biopha.2023.114651
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Canine malignant mesothelioma (cMM) is a rare and drug-resistant malignant tumor. Due to few patients and experimental models, there have not been enough studies to demonstrate the pathogenesis of the disease and novel effective treatment for cMM. Since cMM resembles human MM (hMM) in histopathological characteristics, it is also considered a promising research model of hMM. Compared with conventional 2-dimensional (2D) culture methods, 3-dimensional (3D) organoid culture can recapitulate the properties of original tumor tissues. However, cMM organoids have never been developed. In the present study, we for the first time generated cMM organoids using the pleural effusion samples. Organoids from individual MM dogs were successfully generated. They exhibited the characteristics of MM and expressed mesothelial cell markers, such as WT-1 and mesothelin. The sensitivity to anti-cancer drugs was different in each strain of cMM organoids. RNA sequencing analysis showed cell adhesion molecule pathways were specifically upregulated in cMM organoids compared with their corresponding 2D cultured cells. Among these genes, the expression level of E-cadherin was drastically higher in the organoids than that in the 2D cells. In conclusion, our established cMM organoids might become a new experimental tool to provide new insights into canine and human MM therapy.
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页数:15
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