Tohoku J. Exp. Med., 2011, 224(1)

Osteopontin as a Key Mediator for Vasculogenic Mimicry in Hepatocellular Carcinoma

WENBIN LIU,¹ GELIANG XU,¹ JINLIANG MA,¹ WEIDONG JIA,¹ JIANSHENG LI,¹ KE CHEN,² WEI WANG,¹ CHEN HAO,¹ YONGCANG WANG¹ and XIUJUN WANG¹

¹Centre for the Study of Liver Cancer and Department of Hepatic Surgery, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, P.R. China
²Department of Pathology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, P.R. China

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 HCC. Metastatic MHCC97-H human HCC cells and non-metastatic Hep3B human HCC 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 HCC 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 HCC 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 HCC tissue samples. In conclusion, OPN is required for VM in HCC 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.

keywords —— osteopontin; vasculogenic mimicry; hepatocellular carcinoma; matrix metalloproteinase; plasminogen activator

© 2011 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2011, 224, 29-39

Correspondence: Geliang Xu, Centre for the Study of Liver Cancer and Department of Hepatic Surgery, Affiliated Anhui Provincial Hospital, Anhui Medical University, No. 17, Lujiang Road, Hefei 230001, P.R. China.

e-mail: xugeliang2007@sohu.com or xugeliang2007@163.com