title: Variable asialoglycoprotein receptor 1 expression in liver disease: Implications for therapeutic intervention.
abstract: OBJECTIVE
  One of the most promising strategies for the treatment of liver diseases is targeted drug delivery via the asialoglycoprotein receptor (ASGPR). The success of this approach heavily depends on the ASGPR expression level on parenchymal liver cells. In this study, we assessed the mRNA and protein expression levels of the major receptor subunit, ASGR1, in hepatocytes both in vitro and in vivo.
  
  
  METHODS
  In vitro, various liver cancer-derived cell lines were evaluated. In vivo, we screened the ASGR1 mRNA on 59 hepatocellular carcinoma and matched non-neoplastic tissue using RNA microarray. In addition, 350 human liver specimens of patients with hepatocellular carcinoma or non-neoplastic liver diseases were screened for ASGR1 protein level using tissue microarray analysis.
  
  
  RESULTS
  Our data reveal that the ASGR1 mRNA expression directly correlates with the protein level. We demonstrate that the ASGR1 expression is upregulated in cirrhotic specimens and is significantly decreased with increasing hepatocellular carcinoma grade.
  
  
  CONCLUSIONS
  Because the ASGR1 expression levels are variable between patients, our findings suggest that ASGPR-based targeting strategies should be combined with ASGPR-companion diagnostics to maximize clinical benefit.
authors.affiliation: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Witzigmann
authors.affiliation: Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Quagliata
authors.affiliation: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Schenk
authors.affiliation: Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Quintavalle
authors.affiliation: Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.affiliation: Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
keywords: asialoglycoprotein receptor; drug delivery; hepatocyte; liver disease; nanomedicine