title: Selective portal vein injection for the design of syngeneic models of liver malignancy.
abstract: Liver metastases are the most frequent cause of death due to colorectal cancer (CRC). Syngeneic orthotopic animal models, based on the grafting of cancer cells or tissue in host liver, are efficient systems for studying liver tumors and their (patho)physiological environment. Here we describe selective portal vein injection as a novel tool to generate syngeneic orthotopic models of liver tumors that avoid most of the weaknesses of existing syngeneic models. By combining portal vein injection of cancer cells with the selective clamping of distal liver lobes, tumor growth is limited to specific lobes. When applied on MC-38 CRC cells and their mouse host C57BL6, selective portal vein injection leads with 100% penetrance to MRI-detectable tumors within 1 wk, followed by a steady growth until the time of death (survival ∼7 wk) in the absence of extrahepatic disease. Similar results were obtained using CT-26 cells and their syngeneic Balb/c hosts. As a proof of principle, lobe-restricted liver tumors were also generated using Hepa1-6 (C57BL6-syngeneic) and TIB-75 (Balb/c-syngeneic) hepatocellular cancer cells, demonstrating the general applicability of selective portal vein injection for the induction of malignant liver tumors. Selective portal vein injection is technically straightforward, enables liver invasion via anatomical routes, preserves liver function, and provides unaffected liver tissue. The tumor models are reproducible and highly penetrant, with survival mainly dependent on the growth of lobe-restricted liver malignancy. These models enable biological studies and preclinical testing within short periods of time.
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Perparim
authors.initials: P
authors.lastname: Limani
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Borgeaud
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Linecker
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Tschuor
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kachaylo
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schlegel
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Jae-Hwi
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Udo
authors.initials: U
authors.lastname: Ungethüm
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Montani
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Humar
authors.affiliation: Laboratory of the Swiss Hepato-Pancreatico-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland; and clavien@access.uzh.ch.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000379:methods*; D011169:Portal Vein
keywords: colorectal cancer; fibrosis; hepatocellular carcinoma; metastasis; murine model of liver cancer