Shirakami Yohei, Kato Junichi, Ohnishi Masaya, Taguchi Daisuke, Maeda Toshihide, Ideta Takayasu, Kubota Masaya, Sakai Hiroyasu, Tomita Hiroyuki, Tanaka Takuji, Shimizu Masahito
Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Int J Mol Sci. 2023 Sep 26;24(19):14581. doi: 10.3390/ijms241914581.
Cholangiocarcinoma is the second most common primary cancer of the liver and has a poor prognosis. Various animal models, including carcinogen-induced and genetically engineered rodent models, have been established to clarify the mechanisms underlying cholangiocarcinoma development. In the present study, we developed a novel mouse model of malignant lesions in the biliary ducts induced by the administration of the carcinogen azoxymethane to obese C57BLKS/J-db/db mice. A histopathological analysis revealed that the biliary tract lesions in the liver appeared to be an intrahepatic cholangiocarcinoma with higher tumor incidence, shorter experimental duration, and a markedly increased incidence in obese mice. Molecular markers analyzed using a microarray and a qPCR indicated that the cancerous lesions originated from the cholangiocytes and developed in the inflamed livers. These findings indicated that this is a novel mouse model of intrahepatic cholangiocarcinoma in the context of steatohepatitis. This model can be used to provide a better understanding of the pathogenic mechanisms of cholangiocarcinoma and to develop novel therapeutic strategies for this malignancy.
胆管癌是第二常见的原发性肝癌，预后较差。为阐明胆管癌发生的潜在机制，已建立了多种动物模型，包括致癌物诱导的和基因工程啮齿动物模型。在本研究中，我们通过给肥胖的C57BLKS/J-db/db小鼠施用致癌物偶氮甲烷，开发了一种新型的胆管恶性病变小鼠模型。组织病理学分析显示，肝脏中的胆道病变似乎是肝内胆管癌，其肿瘤发生率更高、实验持续时间更短，且在肥胖小鼠中的发生率显著增加。使用微阵列和qPCR分析的分子标志物表明，癌性病变起源于胆管细胞，并在发炎的肝脏中发展。这些发现表明，这是一种在脂肪性肝炎背景下的新型肝内胆管癌小鼠模型。该模型可用于更好地理解胆管癌的致病机制，并为这种恶性肿瘤开发新的治疗策略。
