title: Core2 O-glycan-expressing prostate cancer cells are resistant to NK             cell immunity.
abstract: Core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N-acetylglucosamine branch in the O-glycans (core2 O-glycans) of cell surface glycoproteins. We previously revealed that the expression of C2GnT is positively correlated with poor prognosis in prostate cancer patients. However, the detailed mechanisms underlying their poor prognosis remain unclear. In the current study, we report that the core2 O-glycans carried by the surface MUC1 glycoproteins of prostate cancer cells play an important role in the evasion of NK cell immunity. In C2GnT‑expressing prostate cancer cells, the MUC1 core2 O-glycans are modified with poly-N-acetyllactosamine. MUC1 glycoproteins carrying poly-N-acetyllactosamine attenuated the interaction of the cancer cells with NK cells, resulting in decreased secretion of granzyme B by the NK cells. Poly‑N‑acetyllactosamine also interfered with the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to access the cancer cell surface. These effects of poly-N-acetyllactosamine on NK cells render C2GnT-expressing prostate cancer cells resistant to NK cell cytotoxicity. By contrast, C2GnT-deficient prostate cancer cells carrying a lower amount of poly-N-acetyllactosamine than the C2GnT-expressing prostate cancer cells were significantly more susceptible to NK cell cytotoxicity. Our results strongly suggest that C2GnT-expressing prostate cancer cells evade NK cell immunity and survive longer in the host blood circulation, thereby resulting in the promotion of prostate cancer metastasis.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of                     Medicine, Hirosaki 036-8562, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Okamoto
authors.forename: Mihoko Sutoh
authors.initials: MS
authors.lastname: Yoneyama
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: 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; D002470:Cell Survival / Q000187:drug effects; D006031:Glycosylation; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D018396:Mucin-1 / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D011134:Polysaccharides; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C037199:poly-N-acetyllactosamine; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; D053804:Granzymes