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MRC2 expression correlates with TGFβ1 and survival in hepatocellular carcinoma.

Gai X, Tu K, Lu Z, Zheng X - Int J Mol Sci (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. xhgai.xjtu@gmail.com.

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.

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(a) (I) The representative immunohistochemistry (IHC) staining of MRC2 in HCC tissues. MRC2 protein located in both cell membrane (black arrow) and cytoplasm (white arrow); (II) The representative IHC staining of MRC2 in adjacent liver tissues; (III) The negative staining of MRC2 in HCC tissues; (b) The western immunoblotting results of MRC2 in 3 pairs of representative HCC tissues (T) and adjacent liver tissues (N); (c) The IHC scores of MRC2 in HCC tissues were significantly higher than one in adjacent liver tissues (p < 0.001); and (d) The comparison of Kaplan–Meier survival curves showed that patients with higher MRC2 expression in HCC tissues had worse prognosis after liver resection (HR = 3.071; 95% CI: 1.357, 6.951; p = 0.007).
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ijms-15-15011-f001: (a) (I) The representative immunohistochemistry (IHC) staining of MRC2 in HCC tissues. MRC2 protein located in both cell membrane (black arrow) and cytoplasm (white arrow); (II) The representative IHC staining of MRC2 in adjacent liver tissues; (III) The negative staining of MRC2 in HCC tissues; (b) The western immunoblotting results of MRC2 in 3 pairs of representative HCC tissues (T) and adjacent liver tissues (N); (c) The IHC scores of MRC2 in HCC tissues were significantly higher than one in adjacent liver tissues (p < 0.001); and (d) The comparison of Kaplan–Meier survival curves showed that patients with higher MRC2 expression in HCC tissues had worse prognosis after liver resection (HR = 3.071; 95% CI: 1.357, 6.951; p = 0.007).

Mentions: To observe MRC2 expression in HCC, immunohistochemistry (IHC) staining assays were carried out and it was found that MRC2 protein located in both cell membrane and cytoplasm, as shown in Figure 1a. By analyzing the IHC score using the Mann–Whitney U test, we found that MRC2 expression in HCC tissues was significantly higher than one in adjacent liver tissues (p < 0.001; Figure 1c). We also examined MRC2 expression by western immunoblotting in 3 pairs of representative HCC tissues and adjacent liver tissues. As shown in Figure 1b, there was significantly more MRC2 expression in HCC tissues than in adjacent liver tissues. The relationship between MRC2 and the clinicopathological parameters of the 96 HCCs was statistically assessed and the results were listed in Table 1. The expression of MRC2 was significantly associated with intrahepatic metastases (r = 0.485, p = 0.005) and portal vein invasion (r = 0.214, p = 0.002). However, there was no significant correlation between MRC2 expression in HCC tissues and gender (r = −0.16, p = 0.062), age (r = 0.344, p = 0.121), HBV infection (r = 0.312, p = 0.075), liver cirrhosis (r = 0.12, p = 0.063), serumα-fetoprotein (AFP) level (r = 0.322, p = 0.130), tumor size (r = 0.271, p = 0.091), Edmonson–Steiner classification (r = 0.332, p = 0.130) and vasculature invasion (r = 0.070, p = 0.071).


MRC2 expression correlates with TGFβ1 and survival in hepatocellular carcinoma.

Gai X, Tu K, Lu Z, Zheng X - Int J Mol Sci (2014)

(a) (I) The representative immunohistochemistry (IHC) staining of MRC2 in HCC tissues. MRC2 protein located in both cell membrane (black arrow) and cytoplasm (white arrow); (II) The representative IHC staining of MRC2 in adjacent liver tissues; (III) The negative staining of MRC2 in HCC tissues; (b) The western immunoblotting results of MRC2 in 3 pairs of representative HCC tissues (T) and adjacent liver tissues (N); (c) The IHC scores of MRC2 in HCC tissues were significantly higher than one in adjacent liver tissues (p < 0.001); and (d) The comparison of Kaplan–Meier survival curves showed that patients with higher MRC2 expression in HCC tissues had worse prognosis after liver resection (HR = 3.071; 95% CI: 1.357, 6.951; p = 0.007).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4200867&req=5

ijms-15-15011-f001: (a) (I) The representative immunohistochemistry (IHC) staining of MRC2 in HCC tissues. MRC2 protein located in both cell membrane (black arrow) and cytoplasm (white arrow); (II) The representative IHC staining of MRC2 in adjacent liver tissues; (III) The negative staining of MRC2 in HCC tissues; (b) The western immunoblotting results of MRC2 in 3 pairs of representative HCC tissues (T) and adjacent liver tissues (N); (c) The IHC scores of MRC2 in HCC tissues were significantly higher than one in adjacent liver tissues (p < 0.001); and (d) The comparison of Kaplan–Meier survival curves showed that patients with higher MRC2 expression in HCC tissues had worse prognosis after liver resection (HR = 3.071; 95% CI: 1.357, 6.951; p = 0.007).
Mentions: To observe MRC2 expression in HCC, immunohistochemistry (IHC) staining assays were carried out and it was found that MRC2 protein located in both cell membrane and cytoplasm, as shown in Figure 1a. By analyzing the IHC score using the Mann–Whitney U test, we found that MRC2 expression in HCC tissues was significantly higher than one in adjacent liver tissues (p < 0.001; Figure 1c). We also examined MRC2 expression by western immunoblotting in 3 pairs of representative HCC tissues and adjacent liver tissues. As shown in Figure 1b, there was significantly more MRC2 expression in HCC tissues than in adjacent liver tissues. The relationship between MRC2 and the clinicopathological parameters of the 96 HCCs was statistically assessed and the results were listed in Table 1. The expression of MRC2 was significantly associated with intrahepatic metastases (r = 0.485, p = 0.005) and portal vein invasion (r = 0.214, p = 0.002). However, there was no significant correlation between MRC2 expression in HCC tissues and gender (r = −0.16, p = 0.062), age (r = 0.344, p = 0.121), HBV infection (r = 0.312, p = 0.075), liver cirrhosis (r = 0.12, p = 0.063), serumα-fetoprotein (AFP) level (r = 0.322, p = 0.130), tumor size (r = 0.271, p = 0.091), Edmonson–Steiner classification (r = 0.332, p = 0.130) and vasculature invasion (r = 0.070, p = 0.071).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. xhgai.xjtu@gmail.com.

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.

Show MeSH
Related in: MedlinePlus