MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis

Yuichiro Suzuki, Mihoko Sutoh, Shingo Hatakeyama, Kazuyuki Mori, Hayato Yamamoto, Takuya Koie, Hisao Saitoh, Kanemitsu Yamaya, Tomihisa Funyu, Tomonori Habuchi, Yoichi Arai, Minoru Fukuda, Chikara Ohyama, Shigeru Tsuboi

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1831-1838
Number of pages8
JournalInternational journal of oncology
Volume40
Issue number6
DOIs
Publication statusPublished - 2012 Jun

Keywords

  • Bladder tumor
  • Core 2 O-glycans
  • Metastasis
  • Mucin 1
  • Natural killer cell immunity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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