title: Successful establishment of an orthotopic hepatoblastoma in vivo model in NOD/LtSz-scid IL2Rγnull mice.
abstract: Investigation of hepatoblastoma in experimental conditions contributes relevantly to a detailed understanding of tumor biology and the investigation of new treatment approaches. Most systematical analyses currently use subcutaneous xenografts. We established a reproducible intrahepatic model with the hepatoblastoma-cell lines HuH6 and HepT1. The cells were stably transfected with a plasmid vector encoding for Gaussia luciferase. HuH6 and HepT1 were injected intrasplenically in NOD/LtSz-scid IL2Rγnull mice. Mice were splenectomized in order to avoid intrasplenical tumor growth. Multifocal intrahepatic tumor growth was observed in 85% (11/13) of HuH6 tumors and 55% (5/9) of HepT1 tumors. Serum Alpha-fetoprotein and Gaussia luciferase increased 5 weeks after tumor-cell inoculation. Tumors were detected by MRI at this time point. Immunhistochemical analysis such as vascularity (CD31), proliferation index (Ki-67), cytokeratin 7 and distribution of β-catenin in intrahepatic tumors were different to subcutaneous tumors. We established a reproducible xenograft model for intrahepatic hepatoblastoma growth with a high tumor incidence. Monitoring of tumor cell viability was optimized by measuring GLuc. This model enables further experimental investigations of HB in a more physiological milieu as emphasized by the β-catenin distribution.
authors.affiliation: Department of Pediatric Surgery, Children's University Hospital Tuebingen, Tuebingen, Germany. verenaellerkamp@googlemail.com
authors.forename: Verena
authors.initials: V
authors.lastname: Ellerkamp
authors.forename: Sorin
authors.initials: S
authors.lastname: Armeanu-Ebinger
authors.forename: Julia
authors.initials: J
authors.lastname: Wenz
authors.forename: Steven W
authors.initials: SW
authors.lastname: Warmann
authors.forename: Juergen
authors.initials: J
authors.lastname: Schäfer
authors.forename: Peter
authors.initials: P
authors.lastname: Ruck
authors.forename: Joerg
authors.initials: J
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018197:Hepatoblastoma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000509:alpha-Fetoproteins