Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma

Chemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of E...

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Main Authors: Elisabeth M. Haberl, Susanne Feder, Rebekka Pohl, Lisa Rein-Fischboeck, Kerstin Dürholz, Laura Eichelberger, Josef Wanninger, Thomas S. Weiss, Christa Buechler
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/10/2967
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author Elisabeth M. Haberl
Susanne Feder
Rebekka Pohl
Lisa Rein-Fischboeck
Kerstin Dürholz
Laura Eichelberger
Josef Wanninger
Thomas S. Weiss
Christa Buechler
author_facet Elisabeth M. Haberl
Susanne Feder
Rebekka Pohl
Lisa Rein-Fischboeck
Kerstin Dürholz
Laura Eichelberger
Josef Wanninger
Thomas S. Weiss
Christa Buechler
author_sort Elisabeth M. Haberl
collection DOAJ
description Chemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of European HCC patients with non-alcoholic fatty liver disease (NAFLD) and patients with unclear disease etiology. A similar regulation was observed in hepatitis B virus (HBV), but not in hepatitis C virus (HCV), related HCC. The apparent discrepancy between the regulation of chemerin in HBV-HCC obtained from our study and recent reports led us to use the chemerin antibodies applied in the previous assays. These antibodies could not equally detect different chemerin isoforms, which were overexpressed in HepG2 cells. Higher chemerin protein in HCC was nevertheless confirmed by the use of all antibodies. Chemerin protein was low in Huh7 and PLC/PRF/5 cells whereas HepG2 and Hep3B cells had chemerin protein similar as primary human hepatocytes. Besides, the anti-tumor effects of retinoids in hepatocyte cell lines did not enclose upregulation of chemerin, which was initially discovered as a tazarotene induced protein in the skin. Finally, protein levels of the chemerin receptor, chemokine-like receptor 1 (CMKLR1), declined in non-viral, and tended to be lower in HBV-HCC tissues suggesting reduced chemerin activity in the tumors. To sum up, our work showed an opposite regulation of chemerin and CMKLR1 in NAFLD and HBV associated HCC. In HCV-HCC neither chemerin nor its receptor were changed in the tumor tissues. Current findings do not support a critical role of total chemerin protein levels in HCC of non-viral and viral etiology. Accordingly, tumor-localized chemerin protein was not associated with tumor-node-metastasis classification.
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spelling doaj.art-a967ebd98c294f518d881d9420bde2122023-11-20T16:57:51ZengMDPI AGCancers2072-66942020-10-011210296710.3390/cancers12102967Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular CarcinomaElisabeth M. Haberl0Susanne Feder1Rebekka Pohl2Lisa Rein-Fischboeck3Kerstin Dürholz4Laura Eichelberger5Josef Wanninger6Thomas S. Weiss7Christa Buechler8Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyChildren’s University Hospital (KUNO), Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyChemerin is protective in experimental models of hepatocellular carcinoma (HCC). Noteworthy, chemerin mRNA and protein were reduced in HCC tissues of Asian patients with mostly hepatitis B disease etiology. The current study nevertheless showed that chemerin protein was induced in tumor tissues of European HCC patients with non-alcoholic fatty liver disease (NAFLD) and patients with unclear disease etiology. A similar regulation was observed in hepatitis B virus (HBV), but not in hepatitis C virus (HCV), related HCC. The apparent discrepancy between the regulation of chemerin in HBV-HCC obtained from our study and recent reports led us to use the chemerin antibodies applied in the previous assays. These antibodies could not equally detect different chemerin isoforms, which were overexpressed in HepG2 cells. Higher chemerin protein in HCC was nevertheless confirmed by the use of all antibodies. Chemerin protein was low in Huh7 and PLC/PRF/5 cells whereas HepG2 and Hep3B cells had chemerin protein similar as primary human hepatocytes. Besides, the anti-tumor effects of retinoids in hepatocyte cell lines did not enclose upregulation of chemerin, which was initially discovered as a tazarotene induced protein in the skin. Finally, protein levels of the chemerin receptor, chemokine-like receptor 1 (CMKLR1), declined in non-viral, and tended to be lower in HBV-HCC tissues suggesting reduced chemerin activity in the tumors. To sum up, our work showed an opposite regulation of chemerin and CMKLR1 in NAFLD and HBV associated HCC. In HCV-HCC neither chemerin nor its receptor were changed in the tumor tissues. Current findings do not support a critical role of total chemerin protein levels in HCC of non-viral and viral etiology. Accordingly, tumor-localized chemerin protein was not associated with tumor-node-metastasis classification.https://www.mdpi.com/2072-6694/12/10/2967CMKLR1hepatitistazarotenechemerin isoform
spellingShingle Elisabeth M. Haberl
Susanne Feder
Rebekka Pohl
Lisa Rein-Fischboeck
Kerstin Dürholz
Laura Eichelberger
Josef Wanninger
Thomas S. Weiss
Christa Buechler
Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
Cancers
CMKLR1
hepatitis
tazarotene
chemerin isoform
title Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
title_full Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
title_fullStr Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
title_full_unstemmed Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
title_short Chemerin Is Induced in Non-Alcoholic Fatty Liver Disease and Hepatitis B-Related Hepatocellular Carcinoma
title_sort chemerin is induced in non alcoholic fatty liver disease and hepatitis b related hepatocellular carcinoma
topic CMKLR1
hepatitis
tazarotene
chemerin isoform
url https://www.mdpi.com/2072-6694/12/10/2967
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