Abstract
BackgroundCD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this study is to investigate the effects of small interfering RNA (siRNA) against CD147 (si-CD147) on hepatocellular carcinoma cells' (SMMC-7721) architecture and functions.MethodsFlow cytometry and western blot assays were employed to detect the transfection efficiency of si-CD147. Confocal microscopy was used to determine the effects of si-CD147 on SMMC-7721 cells' cytoskeleton. Invasion assay, gelatin zymography and cell adhesion assay were employed to investigate the effects of si-CD147 on SMMC-7721 cells' invasion, gelatinase production and cell adhesive abilities. Western blot assay was utilized to detect the effects of si-CD147 on focal adhesion kinase (FAK), vinculiln and mitogen-activated protein kinase (MAPK) expression in SMMC-7721 cells.ResultsDownregulation of CD147 gene induced the alteration of SMMC-7721 cell cytoskeleton including actin, microtubule and vimentin filaments, and inhibited gelatinase production and expression, cells invasion, FAK and vinculin expression. si-CD147 also blocked SMMC-7721 cells adhesion to collagen IV and phosphorylation level of SAPK/JNKs. SAPK/JNKs inhibitor SP600125 inhibited gelatinase production and expression.ConclusionCD147 is required for normal tumor cell architecture and cell invasion. Downregulation of CD147 affects HCC cell structure and function. Moreover, the alteration of cell behavior may be related to SAPK/JNK Pathway. siRNA against CD147 may be a possible new approach for HCC gene therapy.
Highlights
CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs)
Our previous studies have demonstrated that HAb18G/CD147 stimulates fibroblast cells to produce elevated levels of several MMPs, including MMP-1, MMP-2, and MMP-9, which are well known for prompting invasion of hepatocellular carcinoma (HCC) cells and antisense RNA of HAb18G/ CD147 inhibited the invasion of HCC cells in vitro [9]
The results showed that the expression of CD147 in SMMC-7721 cells transfected with si-CD147 was significantly decreased with an inhibitory rate over 80% compared with that in negative control cells (Figure. 1)
Summary
CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). CD147 stimulates production of several matrix metalloproteinases (MMPs) by fibroblasts and endothelial cells [2,3]. Our previous studies have demonstrated that HAb18G/CD147 stimulates fibroblast cells to produce elevated levels of several MMPs, including MMP-1, MMP-2, and MMP-9, which are well known for prompting invasion of hepatocellular carcinoma (HCC) cells and antisense RNA of HAb18G/ CD147 inhibited the invasion of HCC cells in vitro [9]. Our previous work has identified 9 binding peptides by screening a random 12-mer phage peptide library The roles of these peptides inhibiting HCC cell invasion, adhesion and angiogenesis were analyzed [11,12,13]
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