Nitric oxide in papillary thyroid carcinoma: Induction of vascular endothelial growth factor D and correlation with lymph node metastasis
Nitric oxide in papillary thyroid carcinoma: Induction of vascular endothelial growth factor D and correlation with lymph node metastasis
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DOI：
10.1210/jc.2005-1790
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Kakudo, K
中科院分区：
文献类型：
--
作者：
Nakamura, Y;Yasuoka, H;Kakudo, K
目的：血管内皮生长因子-D (VEGF-D) 在甲状腺乳头状癌 (PTC) 中通过淋巴管生成的淋巴结转移中发挥重要作用。尽管 PTC 转移至区域淋巴结的频率很高，但 VEGF-D 表达的调节很大程度上未知。 实验设计：在诱导和/或抑制一氧化氮 (NO) 合成后，在 K1 乳头状甲状腺癌细胞中评估亚硝酸盐/硝酸盐水平和 VEGF-D 产生。在原代人 PTC 中分析硝基酪氨酸的形成，硝基酪氨酸是体内 NO 形成过氧硝酸盐的生物标志物。结果：通过 NO 供体 (Z)-1-[N-(2- 氨乙基)N-(2-氨乙基)氨基] 处理，K1 细胞中亚硝酸盐/硝酸盐和 VEGF-D 的产生增加。 diazen-1-ium-1,2-二醇（DETA NONOate）。 NO合酶抑制剂N(G)-硝基-L-精氨酸甲酯抑制硝酸盐/亚硝酸盐的增加并消除VEGF-D的增加。在 51.8%（56 个中的 29 个）PTC 中观察到高级别硝基酪氨酸染色。硝基酪氨酸水平与 VEGF-D 免疫反应性和淋巴结转移显着相关。结论：我们的数据显示 NO 在体外刺激 VEGF-D 表达中发挥作用。其生物标志物硝基酪氨酸的形成也与人类 PTC 中 VEGF-D 的表达相关。 NO可能通过刺激PTC中的VEGF-D诱导淋巴结转移。
Purpose: Vascular endothelial growth factor-D (VEGF-D) plays an important role in lymph node metastasis via lymphangiogenesis in papillary thyroid carcinoma (PTC). Although PTC metastasizes to regional lymph nodes at a high frequency, the regulation of VEGF-D expression is largely unknown.Experimental Design: Nitrite/nitrate levels and VEGF-D production were assessed in K1 papillary thyroid carcinoma cells after induction and/or inhibition of nitric oxide ( NO) synthesis. Formation of nitrotyrosine, a biomarker for peroxynitrate formation from NO in vivo, was analyzed in primary human PTC.Results: The production of nitrite/nitrate and VEGF-D in K1 cells was increased by treatment with the NO donor, (Z)-1-[N-(2- aminoethyl)N-( 2- ammonioethyl) amino] diazen-1-ium-1,2-diolate ( DETA NONOate). The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester inhibited the increase in nitrate/nitrite and eliminated the increase in VEGF-D. High-grade nitrotyrosine staining was observed in 51.8% ( 29 of 56) of PTCs. Nitrotyrosine levels were significantly correlated with VEGF-D immunoreactivity and lymph node metastasis.Conclusions: Our data showed a role for NO in stimulating VEGF-D expression in vitro. The formation of its biomarker, nitrotyrosine, was also correlated with VEGF-D expression in human PTC. NO may induce lymph node metastasis via VEGF-D stimulation in PTC.