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

Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor.
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DOI:
10.1002/ijc.25117
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发表时间:
2010-09-01
影响因子:
6.4
通讯作者:
Ohyama, Chikara
Ohyama, Chikara
中科院分区:
医学1区
文献类型:
--
作者:
Hatakeyama, Shingo;Kyan, Atsushi;Yamamoto, Hayato;Okamoto, Akiko;Sugiyama, Naoki;Suzuki, Yuichiro;Yoneyama, Takahiro;Hashimoto, Yasuhiro;Koie, Takuya;Yamada, Shigeyuki;Saito, Hideo;Arai, Yoichi;Fukuda, Minoru;Ohyama, Chikara

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我们用抗核心2 N-乙酰氨基葡萄糖转移酶-1(C2 GnT-1)抗体对130例睾丸生殖细胞肿瘤(TGCT)患者的睾丸切除标本进行了免疫组化研究。C2 GnT-1阳性率在Ⅰ期(29.5%,21/71)明显低于高分期(84.7%,50/59)(P < 0.001,χ2检验)。根据组织病理学分型将病例分为胶质瘤和NSGCT时,也存在显著差异。Kaplan-Meier曲线和log rank检验显示,C2 GnT-1阳性的I期乳腺癌患者复发的风险较高(P < 0.001)。I期NSGCT患者也是如此(P < 0.001)。为了确定C2 GnT-1是否促进癌细胞的侵袭行为,用含有C2 GnT-1 cDNA的哺乳动物表达载体稳定转染C2 GnT-1阴性人TGCT细胞系JKT-1。体外试验显示,JKT-1-C2细胞比模拟转染子更具侵袭性,尽管在增殖活性上没有差异。当原位接种到无胸腺裸鼠中时,JKT-1-C2细胞产生较大的睾丸肿瘤,其延伸到腹膜后并伴有肠系膜转移,而模拟转染子产生小肿瘤而无转移(P < 0.01,Mann-Whitney's U检验)。当通过尾静脉注射时,JKT-1-C2细胞产生许多转移性肺病灶。相比之下,模拟转染子产生少量结节(p < 0.01,Mann-Whitney's U检验)。这些结果强烈表明,C2 GnT-1增强TGCT的转移潜力,并可能是TGCT侵袭潜力的可靠生物标志物。
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, 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.
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