期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9070
关键词
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资金
- Fibrolamellar Cancer Foundation (Greenwich, CT, USA)
- Vesta Therapeutics (Bethesda, MD, USA)
- Microscopy Services Laboratory in Pathology and Laboratory Medicine core facility grant (NIH) [P30DK34987]
- Center for Gastrointestinal and Biliary Disease Biology via an NIDDK Grant [DK34987]
- Lineberger Cancer Center grant (NCI) [CA016086]
- Vertex Pharmaceuticals (Cambridge, MA, USA)
- NCI grant [1R21CA182322-01]
- Uehara Memorial Foundation
- NIDDK/NIH grant [R00DK091318-02]
- P.S. R00
- NIH training grants
- UNC Bioinformatics and Computational Biology Curriculum [T32GM067553]
- UNC Molecular Biology of Viral Diseases Pre-doctoral Program [T31AI007419]
- P.S. R00 grant
- NIH [RO1-DK041544]
- MSKCC
- Sapienza University Medical Center (Rome, Italy)
- Agenzia Regionale Del Lazio Per I Trapianti E Le Patologie Connesse, Firb [Rbap10z7fs_001, Rbap10z7fs_004]
- University Sapienza of Rome
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.
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