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

Teppei Okamoto1, Mihoko Sutoh Yoneyama, Shingo Hatakeyama

  • 1Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

Molecular Medicine Reports
|November 21, 2012
PubMed

Insights

Core2 O-glycans on MUC1 glycoproteins, regulated by Core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT), enable prostate cancer cells to evade NK cell immunity. This promotes cancer cell survival and metastasis.

Area of Science:

  • Glycobiology
  • Cancer Immunology
  • Prostate Cancer Research

Background:

  • Core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) modifies O-glycans on cell surface glycoproteins.
  • C2GnT expression correlates with poor prognosis in prostate cancer.
  • Mechanisms of C2GnT-mediated poor prognosis in prostate cancer are not fully understood.

Purpose of the Study:

  • To investigate the role of core2 O-glycans on MUC1 glycoproteins in prostate cancer cell evasion of NK cell immunity.
  • To elucidate the mechanisms by which C2GnT expression influences prostate cancer progression and metastasis.

Main Methods:

  • Analysis of MUC1 glycoproteins and core2 O-glycans in C2GnT-expressing and C2GnT-deficient prostate cancer cells.
  • Assessment of NK cell interactions, granzyme B secretion, and TRAIL-mediated apoptosis.
  • Evaluation of NK cell cytotoxicity against prostate cancer cells with varying C2GnT expression levels.

Main Results:

  • MUC1 glycoproteins on C2GnT-expressing prostate cancer cells are modified with poly-N-acetyllactosamine.
  • Poly-N-acetyllactosamine on MUC1 attenuates NK cell interaction, reduces granzyme B secretion, and hinders TRAIL-induced apoptosis.
  • C2GnT-expressing prostate cancer cells exhibit resistance to NK cell cytotoxicity, while C2GnT-deficient cells are more susceptible.

Conclusions:

  • C2GnT-expressing prostate cancer cells evade NK cell immunity through MUC1 core2 O-glycan modification with poly-N-acetyllactosamine.
  • This evasion mechanism promotes cancer cell survival in circulation and facilitates prostate cancer metastasis.
  • Targeting C2GnT or its glycan products may offer therapeutic strategies for prostate cancer.

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