期刊
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
卷 224, 期 1, 页码 29-39出版社
TOHOKU UNIV MEDICAL PRESS
DOI: 10.1620/tjem.224.29
关键词
osteopontin; vasculogenic mimicry; hepatocellular carcinoma; matrix metalloproteinase; plasminogen activator
资金
- Natural Science Foundation of China [30972892]
- Science and Technology Key Project of Anhui Province [07010302193]
- Anhui Provincial Natural Science Foundation [090413107]
- Anhui Provincial College [KJ2009A178]
- Science and Technological Fund of Anhui Province for Outstanding Youth [08040106818]
- Anhui Provincial 115 Industrial Innovation Program
Osteopontin (OPN) is overexpressed in a variety of cancers including hepatocellular carcinoma (HCC), and is likely involved in the process of vasculogenic mimicry (VM) in some tumor cells. In this study, we explored whether OPN plays a role for VM in HOC. Metastatic MHCC97-H human HOC cells and non-metastatic Hep3B human HOC cells were compared for their abilities to establish VM. Three dimensional-culture assays showed that MHCC97-H cells but not Hep3B cells were able to form the chord-like structure that represents VM. Real-time RT-PCR arrays were used to detect gene expression profiles of the two HOC cell lines in three-dimensional culture. PCR array analyses revealed the increased expression of OPN in MHCC97-H cells forming VM compared with Hep3B cells. Small interfering RNA was employed to investigate whether OPN knockdown could influence VM, and the expression of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) in MHCC97-H cells. OPN knockdown resulted in a significant decrease in the ability of MHCC97-H cells to form VM, which was accompanied by the down-regulation of MMP-2 and uPA expression. Furthermore, human HOC tissue samples were studied by immunohistochemistry to analyze the correlations between VM and the expression of OPN, MMP-2 and uPA. There existed significant positive correlations between VM and the expression of OPN, MMP-2 and uPA in HOC tissue samples. In conclusion, OPN is required for VM in HOC cells, and its action may be associated with activation of MMP-2 and uPA. OPN-targeted therapeutics may be useful for patients with advanced HCC.
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