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A novel strategy for evasion of NK cell immunity by tumours expressing core2 O‐ glycans
Author(s) -
Tsuboi Shigeru,
Sutoh Mihoko,
Hatakeyama Shingo,
Hiraoka Nobuyoshi,
Habuchi Tomonori,
Horikawa Yohei,
Hashimoto Yasuhiro,
Yoneyama Takahiro,
Mori Kazuyuki,
Koie Takuya,
Nakamura Toshiya,
Saitoh Hisao,
Yamaya Kanemitsu,
Funyu Tomihisa,
Fukuda Minoru,
Ohyama Chikara
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.215
Subject(s) - medicine , library science , computer science
The O‐ glycan branching enzyme, core2 β ‐1,6 ‐ N ‐ acetylglucosaminyltransferase (C2GnT), forms O‐ glycans containing an N‐ acetylglucosamine branch connected to N‐ acetylgalactosamine (core2 O‐ glycans) on cell‐surface glycoproteins. Here, we report that upregulation of C2GnT is closely correlated with progression of bladder tumours and that C2GnT‐expressing bladder tumours use a novel strategy to increase their metastatic potential. Our results showed that C2GnT‐expressing bladder tumour cells are highly metastatic due to their high ability to evade NK cell immunity and revealed the molecular mechanism of the immune evasion by C2GnT expression. Engagement of an NK‐activating receptor, NKG2D, by its tumour‐associated ligand, Major histocompatibility complex class I‐related chain A (MICA), is critical to tumour rejection by NK cells. In C2GnT‐expressing bladder tumour cells, poly ‐ N ‐ acetyllactosamine was present on core2 O‐ glycans on MICA, and galectin‐3 bound the NKG2D‐binding site of MICA through this poly ‐ N ‐ acetyllactosamine. Galectin‐3 reduced the affinity of MICA for NKG2D, thereby severely impairing NK cell activation and silencing the NK cells. This new mode of NK cell silencing promotes immune evasion of C2GnT‐expressing bladder tumour cells, resulting in tumour metastasis.