title: MUC1 carrying core 2 O-glycans functions as a molecular shield against             NK cell attack, promoting bladder tumor metastasis.
abstract: Core 2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N-acetylglucosamine branch in O-glycans (core 2 O-glycans) of cell surface glycoproteins. C2GnT-expressing bladder tumors acquire highly metastatic phenotypes by surviving longer in host blood circulation. However, the detailed mechanisms underlying this increased survival remain unclear. In this study, we report that the expression of C2GnT in bladder tumors positively correlates with tumor progression and that bladder tumor cell-surface mucin 1 (MUC1) carrying core 2 O-glycans plays an important role in the evasion from natural killer (NK) cell attack. In C2GnT-expressing bladder tumor cells, heavily core 2 O-glycosylated MUC1 carries poly-N-acetyllactosamine in its O-glycans and galectin-3 binds to MUC1 through this poly-N-acetyllactosamine. The binding of galectin-3 to poly-N-acetyllactosamine in MUC1 core 2 O-glycans attenuates the interaction of the tumor cells with NK cells and interferes with the access of tumor necrosis factor-related apoptosis-inducing ligand to the tumor cell surface. These effects of MUC1 carrying core 2 O-glycans on NK cell attack facilitate C2GnT-expressing tumor cells to evade NK cell immunity and survive longer in host blood circulation. We reveal that MUC1 carrying core 2 O-glycans thus functions as a molecular shield against NK cell attack, thereby promoting bladder tumor metastasis.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of                     Medicine, Hirosaki 036-8562, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Mihoko
authors.initials: M
authors.lastname: Sutoh
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Mori
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.forename: Hisao
authors.initials: H
authors.lastname: Saitoh
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Yamaya
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Funyu
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuboi
mesh_terms: D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005353:Fibronectins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011134:Polysaccharides; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D019139:Tumor Escape; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D005353:Fibronectins; D037502:Galectin 3; C060192:MUC1 protein, human; D018396:Mucin-1; D011134:Polysaccharides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase