Abstract
The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT) in many tumors. Vasculogenic mimicry (VM) is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC). We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation of Runx2 in HepG2 cells, and increased in SMMC7721 cells after Runx2 knockdown. We consistently demonstrated that the downregulation of LGALS3 in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation of LGALS3 in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process.
Highlights
Primary liver cancer is the fifth most common cancer in men and the seventh in women worldwide, and it represents the third most frequent cause of death from cancer [1]
Runx2 Expression Is Associated with the Presence of vasculogenic mimicry (VM) in hepatocellular carcinoma (HCC)
The results indicated that both Vascular endothelial (VE)-cadherin and Galectin-3 expression were increased in the 3D culture system based on the Runx2 transfection of HepG2 cells compared with the control group (Figure 5A)
Summary
Primary liver cancer (i.e., hepatocellular carcinoma, HCC) is the fifth most common cancer in men and the seventh in women worldwide, and it represents the third most frequent cause of death from cancer [1]. A high potential of intrahepatic recurrence and distant metastasis is responsible for the unsatisfying overall prognosis of HCC patients [3]. Apart from the vessel tunnels, which are lined with endothelial cells, Maniotis et al found a new microcirculation mechanism: channels are externally lined with tumor cells, with no endothelial cells in human melanoma [5]. This phenomenon has been termed vasculogenic mimicry (VM). Our research has shown that Runx expression might promote EMT and induce VM in HCC, and Galectin-3 may function intermediately
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