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 nonmetastatic Hep3B human HCC cells were compared for their abilities to establish VM. Three dimensionalculture 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.

Structural and inflammatory heterogeneity in subcutaneous adipose tissue: Relation with liver histopathology in morbid obesity

“…Interestingly, we showed recently that PLAUR is selectively overexpressed in macrophages that infiltrate adipose tissue in obese subjects and we observed that its circulating levels were associated with markers of insulin sensitivity [32]. The plasminogen-activating system has been involved in liver injury such as fibrosis or cancer [33,34]. Whether components of this system produced by dSAT could contribute to aggravated stages of liver alteration in obesity may deserve future consideration.…”

Effects of taurochenodeoxycholic acid on adjuvant arthritis in rats

“…All primers were synthesized by TaKaRa Biotechnology (Japan). Data were analyzed according to the comparative Ct method [17] and were normalized by β-actin expression in each sample. Relative mRNA levels were calculated based on the Ct values, corrected for β-actin expression, according to the equation: 2-△Ct [△Ct = Ct(TNF-α, IL-1β, IL-6 or IL-10) − Ct(β-actin)].…”

Taurochenodeoxycholic acid induces NR8383 cells apoptosis via PKC/JNK-dependent pathway

“…The qPCR was carried out with the specific primers (Table 1). All data were calculated based on the comparative Ct formula (Liu et al, 2011b) and each sample was normalized by β-actin. Relative mRNA expressions were analyzed according to the Ct values, based on the equation: 2 À ΔCt [ΔCt ¼ Ct (PKC, JNK, caspase-3, caspase-8)-Ct (β-actin)].…”