Oncogene-Driven Induction of Orthotopic Cholangiocarcinoma in Mice

Céleste Plantureux; Juliette Paillet; Gwennhael Autret; Maria Pérez-Lanzón; Guido Kroemer; Maria Chiara Maiuri; Jonathan Pol

doi:10.1007/978-1-0716-3694-7_8

Oncogene-Driven Induction of Orthotopic Cholangiocarcinoma in Mice

Methods Mol Biol. 2024:2769:99-108. doi: 10.1007/978-1-0716-3694-7_8.

Authors

Céleste Plantureux^{1

2

3}, Juliette Paillet^{1

2

4

5}, Gwennhael Autret⁶, Maria Pérez-Lanzón^{1

2}, Guido Kroemer^{1

2

7}, Maria Chiara Maiuri^{1

2

8}, Jonathan Pol^{1

2}

Affiliations

¹ Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université Paris Cité, Sorbonne Université, Institut Universitaire de France, Paris, France.
² Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy, Villejuif, France.
³ Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
⁴ Laboratory of Human Lymphohematopoieisis, Imagine Institute, INSERM UMR 1163, Université Paris Cité, Paris, France.
⁵ Smart Immune, Paris, France.
⁶ Plateforme Imageries du Vivant, Université de Paris, PARCC, INSERM, Paris, France.
⁷ Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
⁸ Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, Naples, Italy.

PMID: 38315392
DOI: 10.1007/978-1-0716-3694-7_8

Abstract

Cholangiocarcinoma (CCA) is a malignancy affecting the epithelial cells that line the bile ducts. This cancer shows a poor prognosis and current treatments remain inefficient. Orthotopic CCA mouse models are useful for the development of innovative therapeutic strategies. Here, we describe an orthotopic model of intrahepatic CCA that can be easily induced in mice within 5 weeks at a high incidence. It is achieved by expressing two oncogenes, namely, (i) the intracellular domain of the Notch1 receptor (NICD) and (ii) AKT, in hepatocytes by means of the sleeping beauty transposon system. These plasmid vectors are delivered by hydrodynamic injection into the tail vein. The present chapter also describes how to perform magnetic resonance imaging (MRI) of the livers to visualize intrahepatic CCA nodules.

Keywords: Bile duct cancer; Cholangiocarcinoma; Hydrodynamic injection; Magnetic resonance imaging; Orthotopic model.

MeSH terms

Animals
Bile Duct Neoplasms* / genetics
Bile Ducts, Intrahepatic
Cholangiocarcinoma* / genetics
Liver / pathology
Mice
Oncogenes / genetics