IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9070.html
   My bibliography  Save this article

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

Author

Listed:
  • Tsunekazu Oikawa

    (Department of Cell Biology and Physiology
    Program in Molecular Biology and Biotechnology
    Lineberger Comprehensive Cancer Center)

  • Eliane Wauthier

    (Department of Cell Biology and Physiology
    Program in Molecular Biology and Biotechnology
    Lineberger Comprehensive Cancer Center)

  • Timothy A. Dinh

    (Department of Genetics
    Curriculum in Genetics and Molecular Biology
    MD-PhD Program, UNC School of Medicine)

  • Sara R. Selitsky

    (Department of Genetics
    Curriculum in Bioinformatics and Computational Biology, UNC School of Medicine)

  • Andrea Reyna-Neyra

    (Yale University School of Medicine)

  • Guido Carpino

    (Human and Health Sciences, University of Rome ‘Foro Italico’)

  • Ronald Levine

    (Greenwich Hospital
    Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510 USA)

  • Vincenzo Cardinale

    (Fondazione Eleonora Lorillard Spencer Cenci, Polo Pontino, Viale dell'Universita 37, 00185 Rome, Italy)

  • David Klimstra

    (Memorial Sloan Kettering Cancer Center)

  • Eugenio Gaudio

    (Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome)

  • Domenico Alvaro

    (Fondazione Eleonora Lorillard Spencer Cenci, Polo Pontino, Viale dell'Universita 37, 00185 Rome, Italy)

  • Nancy Carrasco

    (Yale University School of Medicine)

  • Praveen Sethupathy

    (Lineberger Comprehensive Cancer Center
    Department of Genetics
    Curriculum in Genetics and Molecular Biology
    Curriculum in Bioinformatics and Computational Biology, UNC School of Medicine)

  • Lola M. Reid

    (Department of Cell Biology and Physiology
    Program in Molecular Biology and Biotechnology
    Lineberger Comprehensive Cancer Center)

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.

Suggested Citation

  • Tsunekazu Oikawa & Eliane Wauthier & Timothy A. Dinh & Sara R. Selitsky & Andrea Reyna-Neyra & Guido Carpino & Ronald Levine & Vincenzo Cardinale & David Klimstra & Eugenio Gaudio & Domenico Alvaro & , 2015. "Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells," Nature Communications, Nature, vol. 6(1), pages 1-17, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9070
    DOI: 10.1038/ncomms9070
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9070
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9070?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Laura Rüland & Francesco Andreatta & Simone Massalini & Susana Chuva de Sousa Lopes & Hans Clevers & Delilah Hendriks & Benedetta Artegiani, 2023. "Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9070. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.