Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma

Molecular Cancer

Research

Romil Saxena¹  Menggang Yu²  Zhenwen Zhao³  Yan Xu³  Hongmiao Sheng⁴  Mary A. Maluccio⁴  Jian-Min Wu⁴  Nicholas J. Skill⁴ 

[1] Clarian Pathology Laboratory, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Medicine, Division of Biostatistics, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Obstetrics and Gynecology, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;Department of Surgery, Indiana University School of Medicine, 46202, Indianapolis, IN, USA;

关键词: Conditioned Medium;    Huh7 Cell;    Hep3B Cell;    Parthenolide;    Liver Cancer Cell Line;   

DOI  :  10.1186/1476-4598-9-71

 received in 2009-07-24, accepted in 2010-03-31,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAutotaxin (ATX) is an extracellular lysophospholipase D that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Both ATX and LPA have been shown to be involved in many cancers. However, the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma (HCC) remain elusive.ResultsIn this study, ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects. ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis. In addition, ATX expression was examined in normal human hepatocytes and liver cancer cell lines. Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did. Proinflammtory cytokine tumor necrosis factor alpha (TNF-α) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells, which led to a corresponding increase in lysophospholipase-D activity. Moreover, we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B (NF-κB) in basal and TNF-α induced ATX expression. Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion.ConclusionsThis report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-α/NF-κB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis.

【 授权许可】

CC BY   
© Wu et al; licensee BioMed Central Ltd. 2010