Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model
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 t...
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MDPI AG
2019-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/5/496 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kulthida Vaeteewoottacharn |
| collection | DOAJ |
| description | 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<sup>-/-</sup>/Jak3<sup>-/-</sup> 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. |
| first_indexed | 2024-03-12T08:01:28Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:01:28Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fb2d3d426f1d4b69b91cb97d1ccb50bd2023-09-02T19:53:18ZengMDPI AGCells2073-44092019-05-018549610.3390/cells8050496cells8050496Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse ModelKulthida Vaeteewoottacharn0Chawalit Pairojkul1Ryusho Kariya2Kanha Muisuk3Kanokwan Imtawil4Yaovalux Chamgramol5Vajarabhongsa Bhudhisawasdi6Narong Khuntikeo7Ake Pugkhem8O-Tur Saeseow9Atit Silsirivanit10Chaisiri Wongkham11Sopit Wongkham12Seiji Okada13Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, JapanCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandDivision of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, JapanDepartment of Forensic Sciences, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Khon Kaen University, Khon Kaen 40002, ThailandDivision of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, JapanCholangiocarcinoma (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<sup>-/-</sup>/Jak3<sup>-/-</sup> 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.https://www.mdpi.com/2073-4409/8/5/496cholangiocarcinomapatient-derived xenograftcell linecancer modelprecision medicine |
| spellingShingle | 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 Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model Cells cholangiocarcinoma patient-derived xenograft cell line cancer model precision medicine |
| title | Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model |
| title_full | Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model |
| title_fullStr | Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model |
| title_full_unstemmed | Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model |
| title_short | Establishment of Highly Transplantable Cholangiocarcinoma Cell Lines from a Patient-Derived Xenograft Mouse Model |
| title_sort | establishment of highly transplantable cholangiocarcinoma cell lines from a patient derived xenograft mouse model |
| topic | cholangiocarcinoma patient-derived xenograft cell line cancer model precision medicine |
| url | https://www.mdpi.com/2073-4409/8/5/496 |
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