Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity

Okamoto,Teppei; Yoneyama,Mihoko  Sutoh; Hatakeyama,Shingo; Mori,Kazuyuki; Yamamoto,Hayato; Koie,Takuya; Saitoh,Hisao; Yamaya,Kanemitsu; Funyu,Tomihisa; Fukuda,Minoru; Ohyama,Chikara; Tsuboi,Shigeru

doi:10.3892/mmr.2012.1189

February 2013 Volume 7 Issue 2

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February 2013 Volume 7 Issue 2

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Article

Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity

Authors:
- Teppei Okamoto
- Mihoko Sutoh Yoneyama
- Shingo Hatakeyama
- Kazuyuki Mori
- Hayato Yamamoto
- Takuya Koie
- Hisao Saitoh
- Kanemitsu Yamaya
- Tomihisa Funyu
- Minoru Fukuda
- Chikara Ohyama
- Shigeru Tsuboi
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Affiliations: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, Department of Urology, Oyokyo Kidney Research Institute, Hirosaki 036-8243, Japan, Department of Biochemistry, Oyokyo Kidney Research Institute, Hirosaki 036-8243, Japan, Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA
Pages: 359-364
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Published online on: November 19, 2012

https://doi.org/10.3892/mmr.2012.1189
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity

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