Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Int J Cancer. 2010 Sep 1;127(5):1052-9. doi: 10.1002/ijc.25117.
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.
我们使用抗核心 2 N-乙酰氨基葡萄糖基转移酶-1（C2GnT-1）抗体对 130 例睾丸生殖细胞肿瘤（TGCT）的睾丸切除术标本进行了免疫组织化学研究。I 期疾病（29.5%，21/71）中 C2GnT-1 阳性率明显低于较高分期（84.7%，50/59）（P<0.001，卡方检验）。根据组织病理学分类将病例分为精原细胞瘤和 NSGCT 时，也发现了这种显著差异。Kaplan-Meier 图和对数秩检验显示，在 I 期精原细胞瘤患者中，C2GnT-1 阳性病例的复发风险更高（P<0.001）。I 期 NSGCT 患者也是如此（P<0.001）。为了确定 C2GnT-1 是否促进癌细胞的侵袭行为，我们使用含有 C2GnT-1 cDNA 的哺乳动物表达载体稳定转染了 C2GnT-1 阴性的人 TGCT 细胞系 JKT-1。体外实验表明，与 mock 转染体相比，JKT-1-C2 细胞具有更强的侵袭性，尽管增殖活性没有差异。当将 JKT-1-C2 细胞原位接种于无胸腺裸鼠时，JKT-1-C2 细胞产生的睾丸肿瘤较大，延伸至腹膜后并伴有肠系膜转移，而 mock 转染体产生的肿瘤较小且无转移（P<0.01，Mann-Whitney U 检验）。当通过尾静脉注射时，JKT-1-C2 细胞产生了许多转移性肺灶。相比之下，mock 转染体产生的结节较少（P<0.01，Mann-Whitney U 检验）。这些结果强烈表明，C2GnT-1 增强了 TGCT 的转移潜能，可能是 TGCT 侵袭潜能的可靠生物标志物。
