Detailed Characterization and Comparison of Mouse Models for Cholangiocarcinoma

Tulessin, Margaret and Beer, Ludwig and Roessler, Stephanie and Beckers, Anika and Castven, Darko and Calvisi, Diego Francesco and Chen, Xin and Lange, Sebastian and Pfarr, Nicole and Marquardt, Jens and Wirtz, Theresa Hildegard and Berres, Marie-Luise and Steiger, Katja and Groll, Tanja and Mogler, Carolin (2025) Detailed Characterization and Comparison of Mouse Models for Cholangiocarcinoma. LABORATORY INVESTIGATION, 105 (12): 104242. ISSN 0023-6837, 1530-0307

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Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy that originates in the bile ducts and is characterized by late-stage diagnosis and limited treatment options. CCA accounts for approximately 10% to 15% of primary liver tumors. Recent genetic studies have shed new light on this disease, exploring CCA's complexity and finding more effective treatment strategies, particularly based on identifying actionable mutations. Various mouse models for CCA have been established; however, the extent to which these models reflect the complexity of human is not well investigated. Therefore, this study aimed to characterize the available mouse models for CCA studies and compare their characteristics, advantages, and challenges in resemblance to human CCA. We applied tissue-based techniques using classical hematoxylin and eosin, Sirius red, and immunohistochemistry of 16 markers for in-depth characterization of tumor cells, and the tumor microenvironment of 11 different mouse models. Our findings demonstrate that CCAs present with various tumor subtypes, tumor growth patterns, morphologic subtypes, and tumor micro-environment activity. Furthermore, we report here that neoplastic lesions other than CCA, such as hepatocellular carcinoma and nonneoplastic changes in the liver parenchyma (eg, steatosis), occur with significant differences among the investigated models. Nine out of 11 investigated models were suitable for CCA studies as they resemble human CCA features. Overall, our data show that mouse models of CCA represent a valid tool to investigate this deadly disease, but they should be carefully selected, depending on the study's aims and targets in advance. (c) 2025 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Item Type: Article
Uncontrolled Keywords: INTRAHEPATIC CHOLANGIOCARCINOMA; CELL-LINES; LIVER; CANCER; DIAGNOSIS; PATHOLOGY; SUBTYPES; UTILITY; animal model; cholangiocarcinoma; genetically engineered mouse; models; liver diseases
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 19 May 2026 09:13
Last Modified: 19 May 2026 09:13
URI: https://pred.uni-regensburg.de/id/eprint/67450

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