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Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approxi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570293/ https://www.ncbi.nlm.nih.gov/pubmed/36233225 http://dx.doi.org/10.3390/ijms231911923 |
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author | Shao, Wenhua Jargalsaikhan, Orgil Ichimura-Shimizu, Mayuko Cai, Qinyi Ogawa, Hirohisa Miyakami, Yuko Atsumi, Kengo Tomita, Mitsuru Sutoh, Mitsuko Toyohara, Shunji Hokao, Ryoji Kudo, Yasusei Oya, Takeshi Tsuneyama, Koichi |
author_facet | Shao, Wenhua Jargalsaikhan, Orgil Ichimura-Shimizu, Mayuko Cai, Qinyi Ogawa, Hirohisa Miyakami, Yuko Atsumi, Kengo Tomita, Mitsuru Sutoh, Mitsuko Toyohara, Shunji Hokao, Ryoji Kudo, Yasusei Oya, Takeshi Tsuneyama, Koichi |
author_sort | Shao, Wenhua |
collection | PubMed |
description | Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard. |
format | Online Article Text |
id | pubmed-9570293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95702932022-10-17 Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice Shao, Wenhua Jargalsaikhan, Orgil Ichimura-Shimizu, Mayuko Cai, Qinyi Ogawa, Hirohisa Miyakami, Yuko Atsumi, Kengo Tomita, Mitsuru Sutoh, Mitsuko Toyohara, Shunji Hokao, Ryoji Kudo, Yasusei Oya, Takeshi Tsuneyama, Koichi Int J Mol Sci Article Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard. MDPI 2022-10-07 /pmc/articles/PMC9570293/ /pubmed/36233225 http://dx.doi.org/10.3390/ijms231911923 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shao, Wenhua Jargalsaikhan, Orgil Ichimura-Shimizu, Mayuko Cai, Qinyi Ogawa, Hirohisa Miyakami, Yuko Atsumi, Kengo Tomita, Mitsuru Sutoh, Mitsuko Toyohara, Shunji Hokao, Ryoji Kudo, Yasusei Oya, Takeshi Tsuneyama, Koichi Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title | Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title_full | Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title_fullStr | Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title_full_unstemmed | Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title_short | Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice |
title_sort | spontaneous occurrence of various types of hepatocellular adenoma in the livers of metabolic syndrome-associated steatohepatitis model tsod mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570293/ https://www.ncbi.nlm.nih.gov/pubmed/36233225 http://dx.doi.org/10.3390/ijms231911923 |
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