Nagashima Yuko, Yamamoto Haru, Elbadawy Mohamed, Ishihara Yusuke, Tsurukami Issei, Abugomaa Amira, Kaneda Masahiro, Yamawaki Hideyuki, Usui Tatsuya, Sasaki Kazuaki
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.
AIRDEC Mini CO., LTD, 1-2-36 Kajino-Cho, Koganei, Tokyo, 184-0002, Japan.
Sci Rep. 2025 Feb 19;15(1):6108. doi: 10.1038/s41598-025-90623-x.
Canine apocrine gland anal sac adenocarcinoma (AGASACA) is a rare, malignant tumor in dogs. To date, few cell lines are available and used to establish the current treatment protocols. Organoids are three-dimensional cell cultures derived mainly from stem cells and can reproduce tissue's epithelial structure, function, and genetics, and thus, of great promise in precision medicine. In the current investigation, 10 AGASACA organoid lines were developed from surgically removed tissues of AGASACA-affected dogs and analyzed for comparison with the original tissues. AGASACA organoids were successfully generated from all cases and were positive for CK7, HER2, p53, p63, VEGF, and Ki67, and negative for CK20, consistent with previous reports in dogs and humans. Electron microscopic imaging of AGASACA organoids showed organelles, including numerous granules and fat droplets that characterize apocrine gland cells. AGASACA organoids were tumorigenic in vivo in immunodeficient mice. In addition, treatment of the AGASACA organoids with carboplatin, mitoxantrone, toceranib, and lapatinib revealed different sensitivity profiles among lineages, with carboplatin and lapatinib, in particular, being divided into sensitive and resistant ones. In contrast, mitoxantrone and toceranib showed generally high efficacy in all organoids. In conclusion, our established AGASACA organoids have the potential to be an experimental tool for the development of novel therapies for canine and human apocrine gland adenocarcinoma.
犬顶泌汗腺肛门囊腺癌（AGASACA）是犬类中一种罕见的恶性肿瘤。迄今为止，可用的细胞系很少，且用于建立当前的治疗方案。类器官是主要源自干细胞的三维细胞培养物，能够重现组织的上皮结构、功能和遗传学，因此在精准医学中具有巨大潜力。在当前的研究中，从受AGASACA影响的犬的手术切除组织中培养出10个AGASACA类器官系，并进行分析以与原始组织进行比较。所有病例均成功培养出AGASACA类器官，其CK7、HER2、p53、p63、VEGF和Ki67呈阳性，CK20呈阴性，这与之前犬类和人类的报道一致。AGASACA类器官的电子显微镜成像显示出细胞器，包括许多具有顶泌汗腺细胞特征的颗粒和脂肪滴。AGASACA类器官在免疫缺陷小鼠体内具有致瘤性。此外，用卡铂、米托蒽醌、托西拉尼和拉帕替尼处理AGASACA类器官后发现，不同谱系之间的敏感性不同，特别是卡铂和拉帕替尼分为敏感和耐药两类。相比之下，米托蒽醌和托西拉尼在所有类器官中通常显示出较高的疗效。总之，我们建立的AGASACA类器官有潜力成为开发犬类和人类顶泌汗腺腺癌新疗法的实验工具。
