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神经纤毛蛋白-2 在甲状腺乳头状癌中的表达:与 VEGF-D 表达、淋巴结转移和 VEGF-D 诱导的侵袭性癌细胞表型的相关性。

Neuropilin-2 expression in papillary thyroid carcinoma: correlation with VEGF-D expression, lymph node metastasis, and VEGF-D-induced aggressive cancer cell phenotype.

机构信息

Department of Clinical Laboratory Medicine, Wakayama Medical University, 811-1, Kimiidera, 641-8509 Wakayama City, Japan.

出版信息

J Clin Endocrinol Metab. 2011 Nov;96(11):E1857-61. doi: 10.1210/jc.2011-1180. Epub 2011 Aug 31.

DOI:10.1210/jc.2011-1180
PMID:21880798
Abstract

CONTEXT

Neuropilin-2 (Nrp2) is a coreceptor for vascular endothelial growth factor-D (VEGF-D) that is expressed on the surface of endothelial cells. Recently, Nrp2 was shown to play a role in lymph node metastasis and promotion of cancer cell migration. VEGF-D also promotes lymphangiogenesis, which in turn promotes tumor metastasis.

OBJECTIVE

The aim was to study the role of neuropilin-2 in lymph node metastasis in human papillary thyroid carcinoma (PTC).

DESIGN

Expression of Nrp2 was studied by immunohistochemistry and the relationship between Nrp2 expression and lymph node metastasis, VEGF-D expression and other established clinicopathological variables were analyzed in PTC. The effects of neutralizing anti-Nrp2 antibody on VEGF-D-induced invasion and migration were assessed in PTC cell lines.

RESULTS

Nrp2 expression was observed in 64.3% (36 of 56) of the PTC patients. Nrp2 expression was significantly correlated with lymph node metastasis (P = 0.0216) and VEGF-D expression (P = 0.0034). VEGF-D was shown to promote filopodia formation and cancer cell migration and invasion by K1 and B-CPAP cells. These responses were significantly blocked by neutralizing anti-Nrp2 antibody.

CONCLUSION

Nrp2 expression was correlated with lymph node metastasis and VEGF-D expression in PTC. Our data also showed a role for Nrp2 in regulating VEGF-D-induced invasion and migration in vitro.

摘要

背景

神经纤毛蛋白-2(Nrp2)是血管内皮生长因子-D(VEGF-D)的核心受体,在血管内皮细胞表面表达。最近,Nrp2 被证明在淋巴结转移和促进癌细胞迁移中发挥作用。VEGF-D 还促进淋巴管生成,进而促进肿瘤转移。

目的

本研究旨在探讨神经纤毛蛋白-2(Nrp2)在人甲状腺乳头状癌(PTC)淋巴结转移中的作用。

设计

通过免疫组织化学研究 Nrp2 的表达,并分析 Nrp2 表达与淋巴结转移、VEGF-D 表达与其他已建立的临床病理变量之间的关系在 PTC 中。在 PTC 细胞系中评估中和抗-Nrp2 抗体对 VEGF-D 诱导的侵袭和迁移的影响。

结果

在 56 例 PTC 患者中,观察到 64.3%(36/56)的患者 Nrp2 表达。Nrp2 表达与淋巴结转移(P=0.0216)和 VEGF-D 表达(P=0.0034)显著相关。VEGF-D 被证明通过 K1 和 B-CPAP 细胞促进伪足形成和癌细胞迁移和侵袭。这些反应被中和抗-Nrp2 抗体显著阻断。

结论

Nrp2 表达与 PTC 中的淋巴结转移和 VEGF-D 表达相关。我们的数据还表明 Nrp2 在调节 VEGF-D 诱导的体外侵袭和迁移中起作用。

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