Abstract
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.
Highlights
Cholangiocarcinoma (CCA) is a rare subtype of liver cancer for which the highest incidence and mortality have been reported in northeastern Thailand [1,2]
patient-derived xenograft (PDX)-derived cell lines developed in this study show some degree of heterogeneity in vitro and in vivo, which areare common in PDX
The cellular heterogeneity and preserved tissue architecture have been confirmed in PDX-derived cell lines and cell line xenografts
Summary
Cholangiocarcinoma (CCA) is a rare subtype of liver cancer for which the highest incidence and mortality have been reported in northeastern Thailand [1,2]. The prognosis of CCA is dismal because of delayed diagnosis and poor response to conventional chemotherapy and targeted treatment [3]. Surgery is the only treatment option that provides a curative outcome [3,4], but limited numbers of the. Cells 2019, 8, 496 patients are candidates [5]. This outcome is influenced by factors such as tumor subtype, complete resection (R0), lymph node involvement, and vascular invasion [6]. It is urgently important to develop a novel CCA treatment
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