Abstract
MRC2 (Mannose Receptor C Type 2) is a constitutively recycling endocytic receptor belonging to the mannose receptor family, which has been found to be closely involved with cancer metastasis. This study attempted to determine MRC2 expression on hepatocellular carcinoma (HCC) and its significance on postsurgical prognosis of HCCs. The expression of both MRC2 and transforming growth factor (TGFβ1) was detected in tumor tissues and adjacent liver tissues from 96 HCCs by immunohistochemistry staining, and it was found that MRC2 expression in HCC tissues was significantly higher than in adjacent liver tissues. HCCs with higher MRC2 expression had worse prognosis after liver resection. Univariate analysis showed that advanced TNM staging of HCC, higher Edmonson-Steiner classification, intrahepatic metastases, portal vein invasion, higher MRC2 and higher TGFβ1 were the poor prognostic factors. Furthermore, multivariate analysis revealed that intrahepatic metastases, higher MRC2 and higher TGFβ1 were the independent prognostic factors. TGFβ1 treatment up-regulated MRC2 expression, cell migration and invasion of Huh7 cells notably. In addition, knockdown of MRC2 repressed the effect of TGFβ1 on cell migration and invasion. These data suggest that MRC2 overexpression predicts poor prognosis of HCCs after liver resection and MRC2 potentially contributed to TGFβ1-driven up-regulation of cell migration and invasion in HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the highly prevalent malignant diseases and is the third leading cause of cancer related death all through the world [1]
By analyzing the IHC score using the Mann–Whitney U test, we found that Mannose Receptor C Type 2 (MRC2) expression in HCC tissues was significantly higher than one in adjacent liver tissues (p < 0.001; Figure 1c)
We examined MRC2 expression by western immunoblotting in 3 pairs of representative HCC tissues and adjacent liver tissues
Summary
Hepatocellular carcinoma (HCC) is one of the highly prevalent malignant diseases and is the third leading cause of cancer related death all through the world [1]. Because there are no typical clinical manifestations and high metastasis capacity at the early stage, most HCC patients cannot receive curative surgical treatments including radical liver resection and liver transplantation. Transforming growth factor (TGFβ1) is a pleiotropic cytokine which contributes to wound healing, angiogenesis, fibrosis and cancer [5]. It was first identified in mammary epithelial development by Daniel and his colleagues in 1987 [6]. The multifunctional activities of TGFβ1 depends on the stage of carcinogenesis In normal epithelia, it acts as tumor repressors through both inhibiting cell proliferation and inducing apoptosis, whereas accelerating progression of established cancers via activating various oncogenic cell signals and inducing EMT directly [11,13,14].
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