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.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Okamoto T,Yoneyama MS,Hatakeyama S,Mori K,Yamamoto H,Koie T,Saitoh H,Yamaya K,Funyu T,Fukuda M,Ohyama C,Tsuboi Sdoi
10.3892/mmr.2012.1189subject
Has Abstractpub_date
2013-02-01 00:00:00pages
359-64issue
2eissn
1791-2997issn
1791-3004journal_volume
7pub_type
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