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Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells.
Oikawa, Tsunekazu; Wauthier, Eliane; Dinh, Timothy A; Selitsky, Sara R; Reyna-Neyra, Andrea; Carpino, Guido; Levine, Ronald; Cardinale, Vincenzo; Klimstra, David; Gaudio, Eugenio; Alvaro, Domenico; Carrasco, Nancy; Sethupathy, Praveen; Reid, Lola M.
Afiliação
  • Oikawa T; Department of Cell Biology and Physiology, Chapel Hill, North Carolina 27599, USA.
  • Wauthier E; Program in Molecular Biology and Biotechnology, Chapel Hill, North Carolina 27599, USA.
  • Dinh TA; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, USA.
  • Selitsky SR; Department of Cell Biology and Physiology, Chapel Hill, North Carolina 27599, USA.
  • Reyna-Neyra A; Program in Molecular Biology and Biotechnology, Chapel Hill, North Carolina 27599, USA.
  • Carpino G; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, USA.
  • Levine R; Department of Genetics, Chapel Hill, North Carolina 27599, USA.
  • Cardinale V; Curriculum in Genetics and Molecular Biology, Chapel Hill, North Carolina 27599, USA.
  • Klimstra D; MD-PhD Program, UNC School of Medicine, Chapel Hill, North Carolina 27599, USA.
  • Gaudio E; Department of Genetics, Chapel Hill, North Carolina 27599, USA.
  • Alvaro D; Curriculum in Bioinformatics and Computational Biology, UNC School of Medicine, Chapel Hill, North Carolina 27599, USA.
  • Carrasco N; Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
  • Sethupathy P; Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome 'Foro Italico', Piazza Lauro De Bosis 6, 00151 Rome, Italy.
  • Reid LM; Greenwich Hospital, 5 Perryridge Road, Greenwich, Connecticut 06830, USA.
Nat Commun ; 6: 8070, 2015 Oct 06.
Article em En | MEDLINE | ID: mdl-26437858
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / RNA Mensageiro / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Carcinoma Hepatocelular / Proteínas Mutantes Quiméricas / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / RNA Mensageiro / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Carcinoma Hepatocelular / Proteínas Mutantes Quiméricas / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos