Journal of Gastroenterology

, Volume 49, Issue 4, pp 702–714 | Cite as

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder

  • Kenichiro Onuki
  • Hiroaki Sugiyama
  • Kazunori Ishige
  • Toru Kawamoto
  • Takehiro Ota
  • Shunichi Ariizumi
  • Masayuki Yamato
  • Shinichi Kadota
  • Kaoru Takeuchi
  • Akiko Ishikawa
  • Masafumi Onodera
  • Kojiro Onizawa
  • Masakazu Yamamoto
  • Eiji Miyoshi
  • Junichi Shoda
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments.

Methods

Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.

Results

Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.

Conclusions

GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Keywords

Gallbladder carcinoma N-Acetylglucosaminyltransferase V Malignant behavior Postsurgical prognosis Tumor cell biology 

Abbreviations

mAb

Monoclonal antibody

GalNAc-T

N-acetylgalactosaminyltransferase

GnT-V

N-acetylglucosaminyltransferase

pT

Pathological tumor stage

Notes

Acknowledgments

Grant support: This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Nos. 22390379, 22591530, 23390318, 23659659, 24390323).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Kenichiro Onuki
    • 1
  • Hiroaki Sugiyama
    • 2
  • Kazunori Ishige
    • 2
  • Toru Kawamoto
    • 1
  • Takehiro Ota
    • 1
  • Shunichi Ariizumi
    • 1
  • Masayuki Yamato
    • 3
  • Shinichi Kadota
    • 4
  • Kaoru Takeuchi
    • 4
  • Akiko Ishikawa
    • 5
  • Masafumi Onodera
    • 6
  • Kojiro Onizawa
    • 7
  • Masakazu Yamamoto
    • 1
  • Eiji Miyoshi
    • 5
  • Junichi Shoda
    • 8
  1. 1.Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Department of Gastroenterology, Division of Biomedical Science, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  3. 3.Institute of Advanced Biomedical Engineering and ScienceTokyo Women’s Medical UniversityTokyoJapan
  4. 4.Department of Infection Biology, Division of Biomedical Science, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  5. 5.Division of Health SciencesOsaka University Graduate School of MedicineSuitaJapan
  6. 6.Department of GeneticsNational Research Institute for Child Health and DevelopmentTokyoJapan
  7. 7.Department of Oral and Maxillofacial Surgery, Division of Biomedical Science, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  8. 8.Medical Science, Division of Clinical Science, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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