Liu Bo-Qian, Bao Zhi-Ye, Zhu Jia-Yi, Liu Hao
Department of Transplant and Hepatobilliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.
Department of Anorectal Surgery, The People's Hospital of Liaoning Province, Shenyang, Liaoning 110000, P.R. China.
Oncol Lett. 2021 Jan;21(1):47. doi: 10.3892/ol.2020.12308. Epub 2020 Nov 17.
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 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 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.
肝细胞癌中的肿瘤微环境可分为细胞成分和非细胞成分。髓源性抑制细胞（MDSCs）是这种微环境的细胞成分，在肝细胞癌的进展中起重要作用。纤维蛋白原样蛋白2（FGL2）已被证明可通过调节各种类型恶性肿瘤中肿瘤微环境的细胞成分来促进肿瘤进展。本研究旨在确定FGL2在肝细胞癌中的表达及其对肿瘤微环境的影响，以确定肝癌治疗的新靶点。采用免疫组织化学和逆转录定量PCR检测FGL2在肝细胞癌中的表达水平及其与人MDSCs表面标志物的相关性。此外，通过稳定转染表达FGL2的慢病毒建立了过表达FGL2的小鼠肝癌细胞系。另外，使用来自过表达FGL2的细胞系的条件培养基培养从小鼠股骨中提取的新鲜骨髓细胞。还建立了原位肝细胞癌小鼠模型。结果表明，肝细胞癌组织中FGL2表达水平与肿瘤大小密切相关。FGL2水平与肝细胞癌中MDSC表面标志物CD11b和CD33的表达水平呈正相关。结果表明，FGL2可以维持骨髓细胞的未分化状态，从而促进MDSC的积累。此外，在原位肝细胞癌小鼠模型中，我们观察到FGL2的过表达可以促进肿瘤生长，并显著增加肿瘤和脾脏中MDSCs的数量。综上所述，这些发现表明FGL2可能通过促进肿瘤微环境中MDSCs的积累来促进肝细胞癌的肿瘤生长。
