The disease relevance of human hepatocellular xenograft models: molecular characterization and review of the literature.
In recent years a number of new therapeutics has been developed that were not general toxins and inhibitors of cell division like classical chemotherapeutics, but were designed to target a specific pathway. A prerequisite for this development was the comprehensive characterization of molecular alterations occurring in human hepatocellular carcinoma (HCC). However, while much knowledge of the molecular pathogenesis of human HCC has been gained, the model systems used to test the functional relevance of these alterations and applied for preclinical evaluation of drug candidates are still poorly characterized. In this paper, we reviewed the literature about several commonly used HCC cell lines and xenotransplantation models and present our own data on the molecular characterization of these. Results obtained demonstrate that it is important to have a sound knowledge of the specific molecular constitution of the experimental model and to carefully evaluate the functional status of the pathway of interest. For this reason, we make the gene expression profiles publicly available to help researchers making an informed decision about which model to use.
Kashofer
K
K
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
Tschernatsch
M M
MM
Mischinger
H J
HJ
Iberer
F
F
Zatloukal
K
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D014183:Transplantation, Heterologous