Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26437858.
- Also identified by DOI 10.1038/ncomms9070 and PMC identifier 4600730.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells--newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies.
Medical subject headings
- Biomarkers, Tumor
- Carcinoma, Hepatocellular
- Gene Expression Regulation, Neoplastic
- Liver Neoplasms
- Mutant Chimeric Proteins
- Neoplastic Stem Cells
- RNA, Messenger