title: Osteopontin as a key mediator for vasculogenic mimicry in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Centre for the Study of Liver Cancer and Department of Hepatic Surgery, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.forename: Geliang
authors.initials: G
authors.lastname: Xu
authors.forename: Jinliang
authors.initials: J
authors.lastname: Ma
authors.forename: Weidong
authors.initials: W
authors.lastname: Jia
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Hao
authors.forename: Yongcang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiujun
authors.initials: X
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D053495:Osteopontin; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9