RRC ID 65051
Author Shen YL, Gan Y, Gao HF, Fan YC, Wang Q, Yuan H, Song YF, Wang JD, Tu H.
Title TNFSF9 exerts an inhibitory effect on hepatocellular carcinoma.
Journal J Dig Dis
Abstract 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.
Volume 18(7)
Pages 395-403
Published 2017-7-1
DOI 10.1111/1751-2980.12489
PMID 28547807
MeSH 4-1BB Ligand / genetics 4-1BB Ligand / pharmacology 4-1BB Ligand / physiology* Animals Carcinoma, Hepatocellular / drug therapy Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Carcinoma, Hepatocellular / secondary Cell Movement / drug effects Cell Movement / physiology Cell Proliferation / drug effects Cell Proliferation / physiology Down-Regulation Humans Liver Neoplasms / drug therapy Liver Neoplasms / metabolism* Liver Neoplasms / pathology Male Mice, Inbred BALB C Neoplasm Invasiveness Real-Time Polymerase Chain Reaction Recombinant Proteins / pharmacology Tumor Cells, Cultured Xenograft Model Antitumor Assays
IF 1.736
Human and Animal Cells HuH-7