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Murine hepatoblast-derived liver tumors resembling human combined hepatocellular-cholangiocarcinoma with stem cell features

Authors
  • Cai, Xiong1, 2
  • Li, Heli3
  • Kaplan, David E.1
  • 1 University of Pennsylvania, 3400 Civic Center Drive, PCAM GI 7S, Philadelphia, PA, 19104-6145, USA , Philadelphia (United States)
  • 2 Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave., Wuhan, 430022, China , Wuhan (China)
  • 3 Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China , Wuhan (China)
Type
Published Article
Journal
Cell & Bioscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Mar 13, 2020
Volume
10
Issue
1
Identifiers
DOI: 10.1186/s13578-020-00395-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundCombined hepatocellular-cholangiocarcinoma (CHC) is a primary hepatic malignancy with heterogeneously combined histological features of putative hepatic progenitor cells (HPC) origin. We describe a mouse model that exhibits the heterogenous histological and phenotypic finding similar to human CHC.MethodsWe injected hepatoblasts isolated from p53−/− C57BL/6 mice into syngeneic wild-type pre-conditioned C57BL/6 mice. We confirmed that p53−/− murine hepatoblasts act as tumor-initiating cells (TICs) that generate CHC both in situ and within metastases. For comparative pathological study, 8 human cases of CHC with stem cell features were recruited by immunohistochemistry and multicolor fluorescence immunostaining.ResultsWe identified corresponding areas in murine tumors matching each WHO criteria-described subtype of human CHC. In both murine and human tumors, HPC-like cells in tumor nests and associated stem cell features/traits are suggested histologically to be the progenitor origin of the cancerConclusionsThe pathological characteristics of murine tumors recapitulate human CHC with stem cell features. These data provide additional comparative pathological evidence that CHC with stem cell features originate from HPCs and validate a model to study this cancer type in vivo.

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