Abstract
Current treatment of paediatric hepatocellular carcinoma (HCC) is often inefficient due to advanced disease at diagnosis and resistance to common drugs. The aim of this study was to generate a cell line derived from a paediatric HCC in order to expand research in this field. We established the HC-AFW1 cell line from a liver neoplasm of a 4-year-old boy through culturing of primary tumor specimens. The cell line has been stable for over one year of culturing and has a doubling time of 40 h. The tumour cells have an epithelial histology and express HCC-associated proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1 and Vimentin. Forty-nine amino acids in exon 3 of β-Catenin that involve the phosphorylation sites of GSK3 were absent and β-Catenin is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. Several alterations of gene copy numbers were detected by genome-wide SNP array. Among the different drugs tested, cisplatin and irinotecan showed effective inhibition of tumour cell growth in a proliferation assay at concentrations below 5 µg/ml. Subcutaneous xenotransplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumours with high levels of serum AFP. Histological analyses of the primary tumour and xenografts included national and international expert pathological review. Consensus reading characterised the primary tumour and the HC-AFW1-derived tumours as HCC. HC-AFW1 is the first cell line derived from a paediatric HCC without a background of viral hepatitis or cirrhosis and represents a valuable tool for investigating the biology of and therapeutic strategies for childhood HCC.
Highlights
Epithelial liver tumours, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), are the most common primary hepatic malignancies in infants and children
We describe the successful establishment of a continuous cell line derived from a child with HCC
We describe the cell line HC-AFW1, as the first paediatric HCC cell line, which was not generated on the background of viral hepatitis or liver cirrhosis
Summary
Epithelial liver tumours, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), are the most common primary hepatic malignancies in infants and children. HCC in children is less common than HB, accounting for approximately 1% of all paediatric cancers in the western hemisphere. Several issues regarding paediatric HCC remain unresolved. The role of chemotherapy and the indication for liver transplantation in the treatment of paediatric HCC are critically debated [4]. The establishment of cell lines and animal models for paediatric epithelial liver tumours is challenging and only a few HB cell lines have been successfully established during recent years [5,6,7]. There is currently no stable in vitro or in vivo model available for paediatric HCC. The in vitro and in vivo model presented here might serve as tool for acquiring additional information and knowledge on this rare but important tumour entity
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