Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model
Kulthida Vaeteewoottacharn,
Chawalit Pairojkul,
Ryusho Kariya,
Kanha Muisuk,
Kanokwan Imtawil,
Yaovalux Chamgramol,
Vajarabhongsa Bhudhisawasdi,
Narong Khuntikeo,
Ake Pugkhem,
O-Tur Saeseow,
Atit Silsirivanit,
Chaisiri Wongkham,
Sopit Wongkham,
Seiji Okada
Affiliations
Kulthida Vaeteewoottacharn
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Chawalit Pairojkul
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Ryusho Kariya
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Kanha Muisuk
Department of Forensic Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Kanokwan Imtawil
Department of Biochemistry, Khon Kaen University, Khon Kaen 40002, Thailand
Yaovalux Chamgramol
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Vajarabhongsa Bhudhisawasdi
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Narong Khuntikeo
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Ake Pugkhem
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
O-Tur Saeseow
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Atit Silsirivanit
Department of Biochemistry, Khon Kaen University, Khon Kaen 40002, Thailand
Chaisiri Wongkham
Department of Biochemistry, Khon Kaen University, Khon Kaen 40002, Thailand
Sopit Wongkham
Department of Biochemistry, Khon Kaen University, Khon Kaen 40002, Thailand
Seiji Okada
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. Recent multi-omics studies revealed the promising targets for CCA treatment; however, limited models for drug discovery are available. This study aimed to develop a patient-derived xenograft (PDX) model as well as PDX-derived cell lines of CCA for future drug screening. From a total of 16 CCA frozen tissues, 75% (eight intrahepatic and four extrahepatic subtypes) were successfully grown and subpassaged in Balb/c Rag-2-/-/Jak3-/- mice. A shorter duration of PDX growth was observed during F0 to F2 transplantation; concomitantly, increased Oct-3/4 and Sox2 were evidenced in 50% and 33%, respectively, of serial PDXs. Only four cell lines were established. The cell lines exhibited either bile duct (KKK-D049 and KKK-D068) or combined hepatobiliary origin (KKK-D131 and KKK-D138). These cell lines acquired high transplantation efficiency in both subcutaneous (100%) and intrasplenic (88%) transplantation models. The subcutaneously transplanted xenograft retained the histological architecture as in the patient tissues. Our models of CCA PDX and PDX-derived cell lines would be a useful platform for CCA precision medicine.
