Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor.
We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anti-core 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, chi(2) 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.
Hatakeyama
Shingo
S
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Kyan
Atsushi
A
Yamamoto
Hayato
H
Okamoto
Akiko
A
Sugiyama
Naoki
N
Suzuki
Yuichiro
Y
Yoneyama
Takahiro
T
Hashimoto
Yasuhiro
Y
Koie
Takuya
T
Yamada
Shigeyuki
S
Saito
Hideo
H
Arai
Yoichi
Y
Fukuda
Minoru
M
Ohyama
Chikara
C
D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009373:Neoplasms, Germ Cell and Embryonal / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009919:Orchiectomy; D011379:Prognosis; D012186:Retroperitoneal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D018239:Seminoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013736:Testicular Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase