Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor

Shingo Hatakeyama, Atsushi Kyan, Hayato Yamamoto, Akiko Okamoto, Naoki Sugiyama, Yuichiro Suzuki, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Shigeyuki Yamada, Hideo Saito, Yoichi Arai, Minoru Fukuda, Chikara Ohyama

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anticore 2 N- acetylglucosaminyltransferase-1 (C2GnT-1) antibody. The incidence of C2GnT-1 positivity in stage I disease (29.5%, 21/71) was significantly lower than that in higher stages (84.7%, 50/59) (P < 0.001, χ2 test). This significant difference was also found when the cases were divided into seminoma and NSGCT according to histopathological classification. Kaplan-Meier plots and the log rank test showed that in the patients with stage I seminoma, C2GnT-1-positive cases had a higher risk for recurrence (P < 0.001). This was also the case with the patients with stage I NSGCT (P < 0.001). To determine whether C2GnT-1 promotes aggressive behavior of cancer cells, a C2GnT-1-negative human TGCT cell line, JKT-1, was stably transfected with a mammalian expression vector containing C2GnT-1 cDNA. In vitro assays revealed that JKT-1-C2 cells are more invasive than mock transfectants, although there are no differences in proliferation activity. When orthotopically inoculated into athymic nude mice, JKT-1-C2 cells produced larger testicular tumors extending to the retroperitoneum with mesenteric metastasis, while mock transfectants produced small tumors without metastasis (P < 0.01, Mann-Whitney's U-test). When injected via the tail vein, JKT-1-C2 cells produced a number of metastatic lung foci. In contrast, mock transfectants produced a small number of nodules (p < 0.01, Mann-Whitney's U-test). These results strongly suggest that C2GnT-1 enhances the metastatic potential of TGCT and may be a reliable biomarker for aggressive potential of TGCT.

Original languageEnglish
Pages (from-to)1052-1059
Number of pages8
JournalInternational Journal of Cancer
Volume127
Issue number5
DOIs
Publication statusPublished - 2010 Sep 1

Keywords

  • Core 2 N-acetylglucosaminyltransferase-1
  • Metastasis
  • Testicular germ cell tumor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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