Heparanase promotes trans-endothelial migration of hepatocarcinoma cells by inducing apoptosis of microvascular endothelial cells.
10.12122/j.issn.1673-4254.2020.08.01
- Author:
Xiaopeng CHEN
1
;
Rui YE
1
;
Dafei DAI
1
;
Yuhai WU
1
;
Yuanlin YU
1
;
Bin CHENG
1
Author Information
1. First Department of Hepatobiliary Surgery, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China.
- Publication Type:Journal Article
- Keywords:
apoptosis;
heparanase;
hepatocellular carcinoma;
microvascular endothelial cells;
trans-endothelial migration
- MeSH:
Animals;
Apoptosis;
Carcinoma, Hepatocellular;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Endothelial Cells;
Gene Expression Regulation, Neoplastic;
Glucuronidase;
Humans;
Liver Neoplasms;
Mice
- From:
Journal of Southern Medical University
2020;40(8):1065-1071
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effect of heparanase (HPSE) on apoptosis of microvascular endothelial cells (MVECs) and trans-endothelial migration of hepatocellular carcinoma (HCC) cells.
METHODS:A HCC cell line with high HPSE expression was selected by real-time quantitative PCR (qRT-PCR) and Western blotting and transefected with a lentiviral vector containing an interfering RNA sequence of HPSE. Transwell migration assay was performed to detect the trans-endothelial migration (TEM) rate of the transfected HCC cells across human umbilical vein endothelial cells (HUVECs). In a Transwell indirect co-culture system, the effect of HPSE silencing in the HCC cells was determined on apoptosis of HUVECs . A nude mouse model of HCC was used to verify the effect of HPSE on apoptosis of MVECs and liver metastasis of the tumor.
RESULTS:HCCLM3 cell line highly expressing HPSE was selected for the experiment. Transfection of the HCC cells with the lentiviral vector for HPSE interference the HCC cells resulted in significantly lowered TEM rate as compared with the cells transfected with the control vector ( < 0.01). In the indirect co-culture system, the survival rate of HUVECs co-cultured with HCCLM3 cells with HPSE interference was significantly higher and their apoptotic index was significantly lower than those in the control group ( < 0.05). Ultrastructural observation showed no obvious apoptosis of HUVECs co-cultured with HCCLM3 cells with HPSE interference but revealed obvious apoptotic changes in the control group. In the animal experiment, the tumor formation rate in the liver was 100% (6/6) in the control group, significantly higher than that in RNAi group (33.3%, 2/6) ( < 0.05). Under optical microscope, necrosis and apoptosis of the MVECs was detected in the liver of the control mice, while the endothelial cells remained almost intact in RNAi group.
CONCLUSIONS:HPSE promotes the metastasis of HCC cells by inducing apoptosis of MVECs.
