Mouse Model for Cholangiocarcinoma from Peribiliary Glands

A good mouse model is mandatory for elucidating carcinogenic mechanisms and identifying the cellular origin of cancer. Although the lack of an appropriate mouse model has hampered investigation of extrahepatic cholangiocarcinoma (ECC), we recently established a novel mouse model of biliary injury-related ECC by ductal cell-specific activation of Kras and deletion of transforming growth factor (TGF) β receptor type 2 and E-cadherin. Using this mouse model, we identified that peribiliary glands, which are considered a biliary epithelial stem cell niche, are potential cellular origins of ECC. Furthermore, we established an extrahepatic biliary organoid-derived xenograft cholangiocarcinoma (CC) model by lentiviral induction of Cre in organoids. This organoid system recreated the in vivo conditions and facilitated analysis of carcinogenesis. In this chapter, we describe the protocol used to establish our mouse model of ECC derived from peribiliary glands and our extrahepatic biliary organoid-derived xenograft model of CC.