Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma - Université de Lille
Article Dans Une Revue Laboratory Investigation; a Journal of Technical Methods and Pathology Année : 2016

Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma

Makoto Ohta
Makoto Ito
  • Fonction : Auteur
Kenji Uchimura
Motohiro Kobayashi

Résumé

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver neoplasm, followed by hepatocellular carcinoma. ICC can be further subclassified as (i) perihilar and (ii) peripheral types, the latter histologically resembling small-sized intrahepatic bile ducts, such as interlobular bile ducts, cholangioles/ductules and the canals of Hering. Cholangiolocellular carcinoma (CoCC), now classified by the World Health Organization as a subtype of combined hepatocellular-cholangiocarcinoma, is currently regarded as a subtype of peripheral-type ICC. The present study was undertaken to determine whether sulfated glycans recognized by the MECA-79 monoclonal antibody could serve as a CoCC marker. Using immunohistochemistry, we show that MECA-79 sulfated glycans are preferentially expressed at the apical membrane of cholangiocytes found in small-sized intrahepatic bile ducts in normal liver and in canalicular structures formed in CoCC. We also report that apical membrane MECA-79 sulfated glycan expression colocalizes with that of mucin 1 (MUC1) core proteins. We also present immunoblotting of Chinese hamster ovary cells overexpressing FLAG-tagged MUC1 to show that MUC1 serves as a MECA-79 scaffold. Furthermore, we report that SSP-25 human ICC cells overexpressing N-acetylglucosamine-6-O-sulfotransferase 2 (GlcNAc6ST-2), but not GlcNAc6ST-1, exhibit membrane expression of MECA-79 sulfated glycans, suggesting that GlcNAc6ST-2 catalyzes MECA-79 epitope biosynthesis in cholangiocytes. Moreover, both wild-type and GlcNAc6ST-1 knockout mice exhibit apical membrane MECA-79 expression in small-sized intrahepatic bile ducts, namely interlobular bile ducts, whereas MECA-79 expression was completely absent in comparable tissues from GlcNAc6ST-1 and GlcNAc6ST-2 double knockout mice. These data collectively indicate that apical membrane localization of MUC1 proteins decorated with GlcNAc6ST-2-dependent MECA-79 sulfated glycans may mark cholangiocytes with cholangiolar/ductular differentiation and could serve as a useful CoCC marker.

Dates et versions

hal-03180456 , version 1 (25-03-2021)

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Citer

Hitomi Hoshino, Makoto Ohta, Makoto Ito, Kenji Uchimura, Yasuhiro Sakai, et al.. Apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma. Laboratory Investigation; a Journal of Technical Methods and Pathology, 2016, Laboratory Investigation; a Journal of Technical Methods and Pathology, 96 (12), pp.1246-1255. ⟨10.1038/labinvest.2016.104⟩. ⟨hal-03180456⟩

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