Related Experiment Video
Updated: Mar 1, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
TNFSF9 exerts an inhibitory effect on hepatocellular carcinoma
Yu Ling Shen1,2, Yu Gan1, Hai Feng Gao3
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Objective:
Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL and CD137L, has been implicated in cancer immunotherapy due to its function as a T-cell co-stimulator. We aimed to investigate the role of TNFSF9 in the cancer pathogenesis in hepatocellular carcinoma (HCC).
Methods:
TNFSF9 expression was examined by immunohistochemistry in 106 pairs of HCC and adjacent non-tumorous tissues, and by quantitative polymerase chain reaction and Western blot in HCC cell lines. The impact of TNFSF9 on the proliferation, migration and invasion of HCC cells was determined using the 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and transwell assays in vitro. We also assessed the influence of TNFSF9 on the growth and metastasis of HCC tumors in an orthotopic mouse model of human HCC.
Results:
TNFSF9 expression was downregulated in approximately 70% of HCC tissues. A decreased expression of TNFSF9 was also consistently observed in all the four HCC cell lines. Either the overexpression of TNFSF9 or treatment with recombinant TNFSF9 protein could significantly inhibit the proliferation, migration and invasion of Huh7 and SMMC-7721 HCC cells in vitro. The inhibitory effect of TNFSF9 on HCC was further confirmed in vivo. Mice orthotopically transplanted with TNFSF9-overexpressing Huh7 cells developed significantly smaller tumors with less intrahepatic metastasis and distant metastasis compared with the control group.
Conclusions:
TNFSF9 may be a tumor suppressor in HCC. Based on its immune stimulatory aspect and the tumor inhibition property, TNFSF9 may be a promising therapeutic target for HCC.
Insights
Tumor necrosis factor superfamily member 9 (TNFSF9) is downregulated in hepatocellular carcinoma (HCC). Overexpressing TNFSF9 inhibits HCC cell growth, migration, and invasion, suggesting its potential as a tumor suppressor and therapeutic target in HCC.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL, is a co-stimulator of T-cells with implications in cancer immunotherapy.
- The role of TNFSF9 in hepatocellular carcinoma (HCC) pathogenesis remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of TNFSF9 in the pathogenesis of HCC.
- To evaluate TNFSF9's potential as a therapeutic target for HCC.
Main Methods:
- TNFSF9 expression was analyzed in 106 HCC tissue pairs and HCC cell lines using immunohistochemistry, quantitative PCR, and Western blot.
- In vitro assays (MTS, transwell) assessed TNFSF9's impact on HCC cell proliferation, migration, and invasion.
- An orthotopic mouse model evaluated TNFSF9's effect on HCC tumor growth and metastasis.
Main Results:
- TNFSF9 expression was downregulated in approximately 70% of HCC tissues and consistently reduced in HCC cell lines.
- Overexpression or recombinant TNFSF9 protein significantly inhibited HCC cell proliferation, migration, and invasion in vitro.
- In vivo studies showed that TNFSF9 overexpression reduced tumor size and metastasis in an orthotopic HCC mouse model.
Conclusions:
- TNFSF9 exhibits tumor-suppressive properties in HCC.
- TNFSF9's immune-stimulatory functions and tumor inhibition potential suggest it as a promising therapeutic target for HCC.
