Journal article
Variable asialoglycoprotein receptor 1 expression in liver disease: Implications for therapeutic intervention.
- Witzigmann D Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Quagliata L Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
- Schenk SH Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Quintavalle C Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
- Terracciano LM Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
- Huwyler J Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- 2015-10-01
Published in:
- Hepatology research : the official journal of the Japan Society of Hepatology. - 2016
English
AIM
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.
CONCLUSION
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.
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.
CONCLUSION
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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1111/hepr.12599
- PMID 26422581
- Persistent URL
- https://sonar.ch/global/documents/92625
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