TNFSF9 exerts an inhibitory effect on hepatocellular carcinoma

Autor: Hong Tu, Hui Yuan, Yu Ling Shen, Jia Dong Wang, Hai Feng Gao, Yu Gan, Ying Chao Fan, Yan Fang Song, Qing Wang
Rok vydání: 2017
Předmět:
Zdroj: Journal of Digestive Diseases. 18:395-403
ISSN: 1751-2972
DOI: 10.1111/1751-2980.12489
Popis: Aim 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 costimulator. However, little is known about its direct impact on cancer development, particularly for solid tumors. Methods The TNFSF9 expression was examined by immunohistochemistry in 106 pairs of hepatocellular carcinoma (HCC) and the adjacent non-HCC tissues, and by quantitative PCR and Western blot in HCC cell lines. The impact of TNFSF9 on the proliferation, migration, and invastion of HCC cell was was determined using the MTS and transwell assays in vitro. We also assessed the influence of TNFSF9 on the growth and metastasis of HCC tumors in orthotopic mice model of human HCC. Results TNFSF9 was downregulated in approximately 70% HCC cases. Consistently, the decreased expression level of TNFSF9 was also observed in 4/4 HCC cell lines. Either overexpression of TNFSF9 or treatment with the 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 the in vivo study. Mice orthotopically transplanted with TNFSF9-overexpressing Huh7 cells developed significantly smaller tumors with less intrahepatic metastasis and distant metastasis compared to the control group. Conclusion TNFSF9 is 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. Copyright © 2017 John Wiley & Sons, Ltd.
Databáze: OpenAIRE
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