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Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree

View Article: PubMed Central - PubMed

ABSTRACT

Cholangiocarcinoma (CC) is a type of relatively rare neoplasm in adenocarcinoma. The characteristics of CCs as well as biliary epithelial cells are heterogeneous at the different portion of the biliary tree. There are two candidate stem/progenitor cells of the biliary tree, i.e., biliary tree stem/progenitor cell (BTSC) at the peribiliary gland (PBG) of large bile ducts and liver stem/progenitor cell (LPC) at the canals of Hering of peripheral small bile duct. Although previous reports suggest that intrahepatic CC (ICC) can arise from such stem/progenitor cells, the characteristic difference between BTSC and LPC in pathological process needs further investigation, and the etiology of CC remains poorly understood. Here we show that Sterile alpha motif domain containing 5 (SAMD5) is exclusively expressed in PBGs of large bile ducts in normal mice. Using a mouse model of cholestatic liver disease, we demonstrated that SAMD5 expression was upregulated in the large bile duct at the hepatic hilum, the extrahepatic bile duct and PBGs, but not in proliferating intrahepatic ductules, suggesting that SAMD5 is expressed in BTSC but not LPC. Intriguingly, human ICCs and extrahepatic CCs exhibited striking nuclear localization of SAMD5 while the normal hilar large bile duct displayed slight-to-moderate expression in cytoplasm. In vitro experiments using siRNA for SAMD5 revealed that SAMD5 expression was associated with the cell cycle regulation of CC cell lines. Conclusion: SAMD5 is a novel marker for PBG but not LPC in mice. In humans, the expression and location of SAMD5 could become a promising diagnostic marker for the cell type as well as malignancy of bile ducts and CCs.

No MeSH data available.


Expression profiles of SAMD5 and EpCAM in extrahepatic bile duct.(A) Double immunostaining of the vertical section of normal common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is clearly detected in PBGs (arrows), but not in the luminal epithelium of normal common bile duct. (B, C) Double immunostaining of the vertical (B) and horizontal (C) sections of DDC-fed common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is highly expressed in both PBGs (arrows) and the luminal epithelium of dilated common bile duct (arrowheads).
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pone.0175355.g003: Expression profiles of SAMD5 and EpCAM in extrahepatic bile duct.(A) Double immunostaining of the vertical section of normal common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is clearly detected in PBGs (arrows), but not in the luminal epithelium of normal common bile duct. (B, C) Double immunostaining of the vertical (B) and horizontal (C) sections of DDC-fed common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is highly expressed in both PBGs (arrows) and the luminal epithelium of dilated common bile duct (arrowheads).

Mentions: Because PBGs are located around the extrahepatic bile duct as well as the hilar large bile duct, we investigated the expression profile of SAMD5 in extrahepatic bile ducts. Intriguingly, IHC analysis of the vertical section of common bile ducts revealed that SAMD5 was exclusively expressed in PBGs of normal extrahepatic bile ducts (Fig 3A). To investigate whether SAMD5 is induced in extrahepatic cholangiocytes like perihilar large bile ducts by cholestatic injury, we performed IHC analysis of extrahepatic bile ducts after DDC treatment. Double staining of vertical and horizontal sections of common bile ducts with anti-SAMD5 and anti-EpCAM antibodies revealed that SAMD5 was highly expressed in not only PBG, but also in the apical region of the columnar cholangiocytes lining dilated common bile ducts (Fig 3B and 3C). These results suggested that SAMD5 is expressed in PBGs under normal condition, but induced in columnar cholangiocytes lining large bile ducts after cholestatic injury.


Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree
Expression profiles of SAMD5 and EpCAM in extrahepatic bile duct.(A) Double immunostaining of the vertical section of normal common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is clearly detected in PBGs (arrows), but not in the luminal epithelium of normal common bile duct. (B, C) Double immunostaining of the vertical (B) and horizontal (C) sections of DDC-fed common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is highly expressed in both PBGs (arrows) and the luminal epithelium of dilated common bile duct (arrowheads).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5384680&req=5

pone.0175355.g003: Expression profiles of SAMD5 and EpCAM in extrahepatic bile duct.(A) Double immunostaining of the vertical section of normal common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is clearly detected in PBGs (arrows), but not in the luminal epithelium of normal common bile duct. (B, C) Double immunostaining of the vertical (B) and horizontal (C) sections of DDC-fed common bile duct with anti-SAMD5 and anti-EpCAM antibodies. SAMD5 is highly expressed in both PBGs (arrows) and the luminal epithelium of dilated common bile duct (arrowheads).
Mentions: Because PBGs are located around the extrahepatic bile duct as well as the hilar large bile duct, we investigated the expression profile of SAMD5 in extrahepatic bile ducts. Intriguingly, IHC analysis of the vertical section of common bile ducts revealed that SAMD5 was exclusively expressed in PBGs of normal extrahepatic bile ducts (Fig 3A). To investigate whether SAMD5 is induced in extrahepatic cholangiocytes like perihilar large bile ducts by cholestatic injury, we performed IHC analysis of extrahepatic bile ducts after DDC treatment. Double staining of vertical and horizontal sections of common bile ducts with anti-SAMD5 and anti-EpCAM antibodies revealed that SAMD5 was highly expressed in not only PBG, but also in the apical region of the columnar cholangiocytes lining dilated common bile ducts (Fig 3B and 3C). These results suggested that SAMD5 is expressed in PBGs under normal condition, but induced in columnar cholangiocytes lining large bile ducts after cholestatic injury.

View Article: PubMed Central - PubMed

ABSTRACT

Cholangiocarcinoma (CC) is a type of relatively rare neoplasm in adenocarcinoma. The characteristics of CCs as well as biliary epithelial cells are heterogeneous at the different portion of the biliary tree. There are two candidate stem/progenitor cells of the biliary tree, i.e., biliary tree stem/progenitor cell (BTSC) at the peribiliary gland (PBG) of large bile ducts and liver stem/progenitor cell (LPC) at the canals of Hering of peripheral small bile duct. Although previous reports suggest that intrahepatic CC (ICC) can arise from such stem/progenitor cells, the characteristic difference between BTSC and LPC in pathological process needs further investigation, and the etiology of CC remains poorly understood. Here we show that Sterile alpha motif domain containing 5 (SAMD5) is exclusively expressed in PBGs of large bile ducts in normal mice. Using a mouse model of cholestatic liver disease, we demonstrated that SAMD5 expression was upregulated in the large bile duct at the hepatic hilum, the extrahepatic bile duct and PBGs, but not in proliferating intrahepatic ductules, suggesting that SAMD5 is expressed in BTSC but not LPC. Intriguingly, human ICCs and extrahepatic CCs exhibited striking nuclear localization of SAMD5 while the normal hilar large bile duct displayed slight-to-moderate expression in cytoplasm. In vitro experiments using siRNA for SAMD5 revealed that SAMD5 expression was associated with the cell cycle regulation of CC cell lines. Conclusion: SAMD5 is a novel marker for PBG but not LPC in mice. In humans, the expression and location of SAMD5 could become a promising diagnostic marker for the cell type as well as malignancy of bile ducts and CCs.

No MeSH data available.