4311

MME

CALLA|CD10|NEP|SFE;membrane metallo-endopeptidase;MME;membrane metallo-endopeptidase

atriopeptidase|common acute lymphocytic leukemia antigen|enkephalinase|membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase)|membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10)|membrane metallo-endopeptidase

3q25.1-q25.2

protein-coding

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 expressHCC-associated proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin,CD10, CD326, HepPar1 and Vimentin. Forty-nine amino acids in exon 3 of beta-Catenin that involve the phosphorylation sites of GSK3 were absent and beta-Catenin is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. Several alterations of gene copy numberswere 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 microg/ml. Subcutaneous xenotransplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growingdedifferentiated tumours with high levels of serum AFP. Histological analyses ofthe 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.