Protective Role of Decorin in Primary Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix, represents a powerful tumor cell growth and migration inhibitor by hindering receptor tyrosine kinases and inducing p21WAF1/CIP1....
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doaj-4efffd2db2264e2ebeb81fc4b147a1282020-11-25T02:10:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-05-011010.3389/fonc.2020.00645515631Protective Role of Decorin in Primary Hepatocellular CarcinomaAndrea Reszegi0Zsolt Horváth1Hajnalka Fehér2Barnabás Wichmann3Péter Tátrai4Ilona Kovalszky5Kornélia Baghy61st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary2nd Department of Internal Medicine, Semmelweis University, Budapest, HungarySolvo Biotechnology, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, HungaryHepatocellular carcinoma (HCC) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix, represents a powerful tumor cell growth and migration inhibitor by hindering receptor tyrosine kinases and inducing p21WAF1/CIP1. In this study, first we tested decorin expression in HCCs utilizing in silico data, as well as formalin fixed paraffin embedded tissue samples of HCC in a tissue microarray (TMA). In silico data revealed that DCN/SMA mRNA ratio is decreased in HCC compared to normal tissues and follows the staging of the disease. Among TMA samples, 52% of HCCs were decorin negative, 33% exhibited low, and 15% high decorin levels corroborating in silico results. In addition, applying conditioned media of hepatoma cells inhibited decorin expression in LX2 stellate cells in vitro. These results raise the possibility that decorin acts as a tumor suppressor in liver cancer and that is why its expression decreased in HCCs. To further test the protective role of decorin, the proteoglycan was overexpressed in a mouse model of hepatocarcinogenesis evoked by thioacetamide (TA). After transfection, the excessive proteoglycan amount was mainly detected in hepatocytes around the central veins. Upon TA-induced hepatocarcinogenesis, the highest tumor count was observed in mice with no decorin production. Decorin gene delivery reduced tumor formation, in parallel with decreased pEGFR, increased pIGF1R levels, and with concomitant induction of pAkt (T308) and phopho-p53, suggesting a novel mechanism of action. Our results suggest the idea that decorin can be utilized as an anti-cancer agent.https://www.frontiersin.org/article/10.3389/fonc.2020.00645/fulldecorin (DCN)hepatocellular carcinomaproteoglycan (PG)hepatocarcinogenesisextracellular matrix (ECM) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Reszegi Zsolt Horváth Hajnalka Fehér Barnabás Wichmann Péter Tátrai Ilona Kovalszky Kornélia Baghy |
spellingShingle |
Andrea Reszegi Zsolt Horváth Hajnalka Fehér Barnabás Wichmann Péter Tátrai Ilona Kovalszky Kornélia Baghy Protective Role of Decorin in Primary Hepatocellular Carcinoma Frontiers in Oncology decorin (DCN) hepatocellular carcinoma proteoglycan (PG) hepatocarcinogenesis extracellular matrix (ECM) |
author_facet |
Andrea Reszegi Zsolt Horváth Hajnalka Fehér Barnabás Wichmann Péter Tátrai Ilona Kovalszky Kornélia Baghy |
author_sort |
Andrea Reszegi |
title |
Protective Role of Decorin in Primary Hepatocellular Carcinoma |
title_short |
Protective Role of Decorin in Primary Hepatocellular Carcinoma |
title_full |
Protective Role of Decorin in Primary Hepatocellular Carcinoma |
title_fullStr |
Protective Role of Decorin in Primary Hepatocellular Carcinoma |
title_full_unstemmed |
Protective Role of Decorin in Primary Hepatocellular Carcinoma |
title_sort |
protective role of decorin in primary hepatocellular carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-05-01 |
description |
Hepatocellular carcinoma (HCC) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix, represents a powerful tumor cell growth and migration inhibitor by hindering receptor tyrosine kinases and inducing p21WAF1/CIP1. In this study, first we tested decorin expression in HCCs utilizing in silico data, as well as formalin fixed paraffin embedded tissue samples of HCC in a tissue microarray (TMA). In silico data revealed that DCN/SMA mRNA ratio is decreased in HCC compared to normal tissues and follows the staging of the disease. Among TMA samples, 52% of HCCs were decorin negative, 33% exhibited low, and 15% high decorin levels corroborating in silico results. In addition, applying conditioned media of hepatoma cells inhibited decorin expression in LX2 stellate cells in vitro. These results raise the possibility that decorin acts as a tumor suppressor in liver cancer and that is why its expression decreased in HCCs. To further test the protective role of decorin, the proteoglycan was overexpressed in a mouse model of hepatocarcinogenesis evoked by thioacetamide (TA). After transfection, the excessive proteoglycan amount was mainly detected in hepatocytes around the central veins. Upon TA-induced hepatocarcinogenesis, the highest tumor count was observed in mice with no decorin production. Decorin gene delivery reduced tumor formation, in parallel with decreased pEGFR, increased pIGF1R levels, and with concomitant induction of pAkt (T308) and phopho-p53, suggesting a novel mechanism of action. Our results suggest the idea that decorin can be utilized as an anti-cancer agent. |
topic |
decorin (DCN) hepatocellular carcinoma proteoglycan (PG) hepatocarcinogenesis extracellular matrix (ECM) |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.00645/full |
work_keys_str_mv |
AT andreareszegi protectiveroleofdecorininprimaryhepatocellularcarcinoma AT zsolthorvath protectiveroleofdecorininprimaryhepatocellularcarcinoma AT hajnalkafeher protectiveroleofdecorininprimaryhepatocellularcarcinoma AT barnabaswichmann protectiveroleofdecorininprimaryhepatocellularcarcinoma AT petertatrai protectiveroleofdecorininprimaryhepatocellularcarcinoma AT ilonakovalszky protectiveroleofdecorininprimaryhepatocellularcarcinoma AT korneliabaghy protectiveroleofdecorininprimaryhepatocellularcarcinoma |
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