Abstract
BackgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recurrence and metastasis after curative resection remain critical obstacles in HCC treatment. CD146 predicted poor prognosis of a variety of cancers including melanoma, breast tumors, prostate cancer, and gastric cancer. However, the role of CD146 in HCC has not yet been systematically explored.MethodsTo investigate the role of CD146 in HCC, we evaluated its expression in HCC tissues and HCC cell lines using real-time PCR and western blotting (WB). Second, we established HCC cell lines that stably overexpressed and interfered CD146 and explored the function of CD146 in HCC in vitro and in vivo. Third, we conducted microarray analysis to investigate the potential mechanism by identifying differentially expressed genes. Last, follow ups were conducted to help uncover the connection of CD146 expression and the prognosis of HCC patients.ResultsWe found that CD146 was overexpressed in HCC tissues and that high CD146 expression predicted poor overall survival time and shorter recurrence period in HCC patients. In vitro and in vivo experiments indicated that CD146 promoted migration and invasion of HCC cell lines. Further study indicated that CD146 promoted epithelial mesenchymal transition (EMT), IL-8 upregulation, and STAT1 downregulation. CD146 was upregulated in HCC tissues and cell lines.ConclusionsCD146 promoted metastasis of HCC cells and predicted poor prognosis of HCC patients. CD146 induced EMT, and IL-8 upregulation and STAT1 downregulation may be the potential underlying mechanism. The exact mechanism still needs further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0313-3) contains supplementary material, which is available to authorized users.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide
The expression of CD146 is upregulated in HCC To investigate the role of CD146 in HCC, we first explored the expression of CD146 in HCC tissues and HCC cell lines
We examined CD146 mRNA levels in 120 paired HCC and peritumoral samples using Real-time polymerase chain reaction (RTPCR) and found that the average expression level of CD146 was significantly higher in HCC than that in peritumoral tissues (Fig. 1a)
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recurrence and metastasis after curative resection remain critical obstacles in HCC treatment. CD146 predicted poor prognosis of a variety of cancers including melanoma, breast tumors, prostate cancer, and gastric cancer. The role of CD146 in HCC has not yet been systematically explored. Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer and the third leading cause of cancer-related mortality in China [1]. Recurrence and metastasis after curative resection are the most challenging burdens for HCC treatment [2]. The underlying mechanism of HCC metastasis is largely unknown. CD146 was first reported in malignant melanomas [3]. CD146 is a 113-kD membrane glycoprotein that contains five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail [4].
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