TY - JOUR
T1 - Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor
AU - Hatakeyama, Shingo
AU - Kyan, Atsushi
AU - Yamamoto, Hayato
AU - Okamoto, Akiko
AU - Sugiyama, Naoki
AU - Suzuki, Yuichiro
AU - Yoneyama, Takahiro
AU - Hashimoto, Yasuhiro
AU - Koie, Takuya
AU - Yamada, Shigeyuki
AU - Saito, Hideo
AU - Arai, Yoichi
AU - Fukuda, Minoru
AU - Ohyama, Chikara
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
KW - Core 2 N-acetylglucosaminyltransferase-1
KW - Metastasis
KW - Testicular germ cell tumor
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U2 - 10.1002/ijc.25117
DO - 10.1002/ijc.25117
M3 - Article
C2 - 20017138
AN - SCOPUS:77955498039
VL - 127
SP - 1052
EP - 1059
JO - International journal of cancer. Journal international du cancer
JF - International journal of cancer. Journal international du cancer
SN - 0020-7136
IS - 5
ER -