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

• Published in: PloS one Vol. 12; no. 4; p. e0175355
• Main Authors: Yagai, Tomoki, Matsui, Satoshi, Harada, Kenichi, Inagaki, Fuyuki F, Saijou, Eiko, Miura, Yasushi, Nakanuma, Yasuni, Miyajima, Atsushi, Tanaka, Minoru
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-04-2017; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Analysis; Animals; Bile; Bile ducts; Biliary tract; Biliary tract cancer; Biliary Tract Neoplasms - metabolism; Biliary Tract Neoplasms - pathology; Biology and Life Sciences; Biotechnology; Canals; Cancer; Cell cycle; Cell growth; Cell Nucleus - metabolism; Cell Proliferation; Cells (biology); Cholangiocarcinoma; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; Cytoplasm; Diagnosis; Diagnostic systems; Epithelial cells; Etiology; Gene expression; Hepatocytes; In vitro methods and tests; Liver; Liver diseases; Localization; Malignancy; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Progenitor cells; Research and Analysis Methods; Rodents; siRNA; Stem cells; Sterile Alpha Motif; Tumorigenesis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0175355

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.
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.