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Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment
The tumor microenvironment in hepatocellular carcinoma can be classified into cellular and non-cellular components. Myeloid-derived suppressor cells (MDSCs) are cellular components of this microenvironment that serve an important role in the progression of hepatocellular carcinoma. Fibrinogen-like p...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709556/ https://www.ncbi.nlm.nih.gov/pubmed/33281958 http://dx.doi.org/10.3892/ol.2020.12308 |
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author | Liu, Bo-Qian Bao, Zhi-Ye Zhu, Jia-Yi Liu, Hao |
author_facet | Liu, Bo-Qian Bao, Zhi-Ye Zhu, Jia-Yi Liu, Hao |
author_sort | Liu, Bo-Qian |
collection | PubMed |
description | The tumor microenvironment in hepatocellular carcinoma can be classified into cellular and non-cellular components. Myeloid-derived suppressor cells (MDSCs) are cellular components of this microenvironment that serve an important role in the progression of hepatocellular carcinoma. Fibrinogen-like protein 2 (FGL2) has been demonstrated to promote tumor progression by regulating cellular components of the tumor microenvironment in various types of malignant tumor. The present study aimed to determine the expression of FGL2 in hepatocellular carcinoma and its effect on the tumor microenvironment in order to determine novel targets for liver cancer treatment. Immunohistochemistry and reverse transcription quantitative PCR were performed to determine the expression level of FGL2 and the correlation with surface markers of human MDSCs in hepatocellular carcinoma. Furthermore, a mouse hepatocellular carcinoma cell line overexpressing FGL2 was established by stable transfection of a lentivirus expressing FGL2. In addition, fresh bone marrow cells extracted from mouse femurs were in vitro cultured using conditioned medium derived from the cell line overexpressing FGL2. An orthotopic hepatocellular carcinoma mouse model was also established. The results demonstrated that FGL2 expression level in hepatocellular carcinoma tissues was closely associated with tumor size. FGL2 level was positively correlated with the expression level of the MDSC surface markers CD11b and CD33 in hepatocellular carcinoma. The in vitro results demonstrated that FGL2 could maintain the undifferentiated state of bone marrow cells, therefore promoting MDSC accumulation. Furthermore, in the orthotopic hepatocellular carcinoma mouse model, we observed that overexpression of FGL2 could promote tumor growth and significantly increase the number of MDSCs in the tumors and spleen. Taken together, these findings suggested that FGL2 may promote hepatocellular carcinoma tumor growth by promoting the accumulation of MDSCs in the tumor microenvironment. |
format | Online Article Text |
id | pubmed-7709556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-77095562020-12-03 Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment Liu, Bo-Qian Bao, Zhi-Ye Zhu, Jia-Yi Liu, Hao Oncol Lett Articles The tumor microenvironment in hepatocellular carcinoma can be classified into cellular and non-cellular components. Myeloid-derived suppressor cells (MDSCs) are cellular components of this microenvironment that serve an important role in the progression of hepatocellular carcinoma. Fibrinogen-like protein 2 (FGL2) has been demonstrated to promote tumor progression by regulating cellular components of the tumor microenvironment in various types of malignant tumor. The present study aimed to determine the expression of FGL2 in hepatocellular carcinoma and its effect on the tumor microenvironment in order to determine novel targets for liver cancer treatment. Immunohistochemistry and reverse transcription quantitative PCR were performed to determine the expression level of FGL2 and the correlation with surface markers of human MDSCs in hepatocellular carcinoma. Furthermore, a mouse hepatocellular carcinoma cell line overexpressing FGL2 was established by stable transfection of a lentivirus expressing FGL2. In addition, fresh bone marrow cells extracted from mouse femurs were in vitro cultured using conditioned medium derived from the cell line overexpressing FGL2. An orthotopic hepatocellular carcinoma mouse model was also established. The results demonstrated that FGL2 expression level in hepatocellular carcinoma tissues was closely associated with tumor size. FGL2 level was positively correlated with the expression level of the MDSC surface markers CD11b and CD33 in hepatocellular carcinoma. The in vitro results demonstrated that FGL2 could maintain the undifferentiated state of bone marrow cells, therefore promoting MDSC accumulation. Furthermore, in the orthotopic hepatocellular carcinoma mouse model, we observed that overexpression of FGL2 could promote tumor growth and significantly increase the number of MDSCs in the tumors and spleen. Taken together, these findings suggested that FGL2 may promote hepatocellular carcinoma tumor growth by promoting the accumulation of MDSCs in the tumor microenvironment. D.A. Spandidos 2021-01 2020-11-17 /pmc/articles/PMC7709556/ /pubmed/33281958 http://dx.doi.org/10.3892/ol.2020.12308 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Bo-Qian Bao, Zhi-Ye Zhu, Jia-Yi Liu, Hao Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title | Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title_full | Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title_fullStr | Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title_full_unstemmed | Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title_short | Fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
title_sort | fibrinogen-like protein 2 promotes the accumulation of myeloid-derived suppressor cells in the hepatocellular carcinoma tumor microenvironment |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709556/ https://www.ncbi.nlm.nih.gov/pubmed/33281958 http://dx.doi.org/10.3892/ol.2020.12308 |
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