Protective Role of Decorin in Primary Hepatocellular Carcinoma
| Autor: | Zsolt Horváth, Andrea Reszegi, Kornélia Baghy, Péter Tátrai, Ilona Kovalszky, Barnabás Wichmann, Hajnalka Fehér |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Decorin lcsh:RC254-282 Receptor tyrosine kinase Extracellular matrix proteoglycan (PG) 03 medical and health sciences 0302 clinical medicine Original Research Tissue microarray biology Chemistry hepatocarcinogenesis Transfection hepatocellular carcinoma HCCS extracellular matrix (ECM) lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens digestive system diseases carbohydrates (lipids) 030104 developmental biology Oncology Proteoglycan 030220 oncology & carcinogenesis Hepatic stellate cell biology.protein Cancer research decorin (DCN) |
| Zdroj: | Frontiers in Oncology, Vol 10 (2020) Frontiers in Oncology |
| DOI: | 10.3389/fonc.2020.00645/full |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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