Abstract 5354: Characterisation of the cell line HC-AFW1 derived from a paediatric hepatocellular carcinoma

Abstract

Abstract Paediatric hepatocellular carcinoma (HCC) has an incidence of 1.5 cases per million children and is linked to viral hepatitis in endemic regions. In Europe childhood HCC mostly arises in otherwise healthy liver and has an unknown ethiology. Current treatment results of HCC are dissatisfactory due to advanced disease at diagnosis and lacking response to chemotherapy. To improve the research of childhood HCC and to address specific therapeutic approaches a preclinical model for childhood HCC is needed. So far, there has been one existing cell line, HepG2, which has lately been discussed controversially as being hepatoblastoma. We established a cell line HC-AFW1 from the tumor of a 5 year old boy. The original tumor histology was characteristic as transitional liver cell tumor including hepatoblastoma and HCC morphology. These histological findings were confirmed through several reference pathology laboratories worldwide. The cell line HC-AFW1 was established by xenotransplantation of original tumor into immuno-deficient mice and re-culturing in vitro. The cell line is in sable culture now for over 8 months with a doubling time of 40 h. Cultured cells present epithelial characteristics and express hepatoma proteins like AFP, glypican 3, E-cadherin, CD10, CD326, HepPar1, Vimentin and Desmin. Catenin beta shows a deletion of 49 amino acids in the exon 3 involving the phosphorylation sites of GSK3 and was detected in cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. This involves chromosomal aberrations found in hepatoblastoma as well as in adult HCC. Several alterations of gene copy numbers were detected by genome wide SNP array. Among different tested drugs cisplatin and irinotecan showed an effective inhibition of tumor cell growth in an MTT assay at concentration below 5 µg/ml. Transplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumors with high levels of serum AFP. This xenotransplants as well as stable cultured cells solely consist of HCC components suggesting a selection of HCC and degeneration of formally hepatoblastoma tumor parts. Therefore, HC-AFW1 is the first paediatric HCC-derived cell line and represents a valuable tool to investigate the biology and therapeutic strategies in childhood HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5354. doi:10.1158/1538-7445.AM2011-5354