Tetraspanin-8 promotes hepatocellular carcinoma metastasis by increasing ADAM12m expression
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Tingting Fang1,*, Jiajia Lin1,*, Yanru Wang2, Guangnan Chen3, Jing Huang2, Jie Chen1, Yan Zhao1, Ruixia Sun1, Chunmin Liang2, Binbin Liu1
1Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P. R. China
2Laboratory of Tumor Immunology, Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China
3The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China
*These authors have contributed equally to this work
Chunmin Liang, email: email@example.com
Binbin Liu, email: firstname.lastname@example.org
Keywords: ADAM12, hepatocellular carcinoma, metastasis, TSPAN8
Received: October 06, 2015 Accepted: April 18, 2016 Published: June 01, 2016
Recent evidence indicates that tetraspanin-8 (TSPAN8) promotes tumor progression and metastasis. In this study, we explored the effects of TSPAN8 and the molecular mechanisms underlying hepatocellular carcinoma (HCC) metastasis using various HCC cell lines, tissues from 149 HCC patients, and animal models of HCC progression. We showed that elevated expression of TSPAN8 promoted HCC invasion in vitro and metastasis in vivo, but did not influence HCC cell proliferation in vitro. Increased TSPAN8 expression in human HCC was predictive of poor survival, and multivariate analyses indicated TSPAN8 expression to be an independent predictor for both postoperative overall survival and relapse-free survival. Importantly, TSPAN8 enhanced HCC invasion and metastasis by increasing ADAM12m expression. We therefore conclude that TSPAN8 and ADAM12m may be useful therapeutic targets for the prevention of HCC progression and metastasis.
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