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.
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.
Authors: Charlotte Bon; Thomas Hofer; Alain Bousquet-Mélou; Mark R Davies; Ben-Fillippo Krippendorff Journal: MAbs Date: 2017-09-06 Impact factor: 5.857
Authors: Dominik Witzigmann; Jayesh A Kulkarni; Jerry Leung; Sam Chen; Pieter R Cullis; Roy van der Meel Journal: Adv Drug Deliv Rev Date: 2020-07-02 Impact factor: 15.470
Authors: Dominik Witzigmann; Philipp Uhl; Sandro Sieber; Christina Kaufman; Tomaz Einfalt; Katrin Schöneweis; Philip Grossen; Jonas Buck; Yi Ni; Susanne H Schenk; Janine Hussner; Henriette E Meyer Zu Schwabedissen; Gabriela Québatte; Walter Mier; Stephan Urban; Jörg Huwyler Journal: Elife Date: 2019-07-23 Impact factor: 8.140
Authors: Jennifer L S Willoughby; Amy Chan; Alfica Sehgal; James S Butler; Jayaprakash K Nair; Tim Racie; Svetlana Shulga-Morskaya; Tuyen Nguyen; Kun Qian; Kristina Yucius; Klaus Charisse; Theo J C van Berkel; Muthiah Manoharan; Kallanthottathil G Rajeev; Martin A Maier; Vasant Jadhav; Tracy S Zimmermann Journal: Mol Ther Date: 2017-09-07 Impact factor: 11.454