Hepatocyte transformation is induced by laminin γ2 monomer
Rattachement africain : jp. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Serum laminin-γ2 monomer (Lm-γ2m) is a potent predictive biomarker for hepatocellular carcinoma (HCC) onset in patients with hepatitis C infection who achieve a sustained virologic response with liver cirrhosis (LC) and for the onset of extrahepatic metastases in early-stage HCC. Although Lm-γ2m involvement in late-stage cancer progression has been well investigated, its precise roles in HCC onset remain to be systematically investigated. Therefore, we analyzed an HCC model, human hepatocytes and cholangiocytes, and surgically resected liver tissues from patients with HCC to understand the roles of Lm-γ2m in HCC onset. Ck-19- and EpCAM-positive hepatic progenitor cells (HPCs) in the liver of pdgf-c transgenic HCC mouse model with ductular reaction showed ectopic expression of Lm-γ2m. Forced expression of Lm-γ2m in hepatocytes adjacent to HPCs resulted in enhanced tumorigenicity, cell proliferation, and migration in immortalized hepatocytes, but not in cholangiocytes in vitro. Further, pharmacological inhibition of epidermal growth factor receptor (EGFR) and c-Jun activator JNK suppressed Lm-γ2m-induced hepatocyte transformation, suggesting the involvement of EGFR/c-Jun signaling in the transformation, leading to HCC development. Finally, immunohistochemical staining of HCC tissues revealed a high level of Lm-γ2 expression in the HPCs of the liver with ductular reaction in normal liver adjacent to HCC tissues. Overall, HPC-derived Lm-γ2m in normal liver with ductular reaction acts as a paracrine growth factor on surrounding hepatocytes and promotes their cellular transformation through the EGFR/c-Jun signaling pathway. Furthermore, this is the first report on Lm-γ2m expression detected in the normal liver with ductular reaction, a human precancerous lesion of HCC.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Hepatocyte transformation is induced by laminin γ2 monomer
- Date Crossref
- 01/07/2024
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Tokyo Institute of Technology Department of Life Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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Kanazawa University Department of Gastroenterology pays non établi dans la noticeUniversité ou école supérieure
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Kanagawa Prefectural Hospital Organization pays non établi dans la noticeÉtablissement de santé
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Kanagawa Cancer Center pays non établi dans la noticeÉtablissement de santé
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Graduate School of Medical Science Department of Gastroenterology pays non établi dans la noticeUniversité ou école supérieure
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Clinical Cancer Proteomics Laboratory pays non établi dans la noticeStructure de recherche
Department of Life Science and Technology — Tokyo Institute of Technology, Department of Gastroenterology — Kanazawa University et Kanagawa Prefectural Hospital Organization, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.