Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer
Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer
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DOI：
10.1002/ar.21096
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发表时间：
2010-05-01
影响因子：
2
通讯作者：
Zhang, Jianguo
中科院分区：
文献类型：
--
作者：
Feng, Yukuan;Wang, Wei;Zhang, Jianguo
血管内皮生长因子（VEGF）-C和VEGF-D通过激活VEGF受体3（VEGFR-3）诱导淋巴管生成，并与肿瘤扩散至淋巴系统有关。淋巴结转移严重影响非小细胞肺癌（NSCLC）患者的临床结局和治疗选择。然而，VEGF-C、VEGF-D与肿瘤（包括NSCLC）淋巴结转移的关系仍存在争议。为探讨淋巴管生成与淋巴结转移的关系，采用免疫组化和实时定量聚合酶链反应（QRT-PCR）方法检测VEGF-C和VEGF-D在NSCLC中的表达。定量RT-PCR结果显示，边缘区VEGF-C和VEGF-D的mRNA表达明显高于瘤中心区，VEGF-D的mRNA表达也明显高于瘤周肺组织。免疫组化结果显示，VEGF-C和VEGF-D蛋白表达均呈异质性。边缘区VEGF-C、VEGF-D高表达组淋巴结转移率高于低表达组。边缘区VEGF-D高表达组淋巴管浸润发生率高。高瘤周淋巴管密度组VEGF-C和VEGF-D mRNA表达高于低瘤周淋巴管密度组。我们的研究提示，VEGF-C和VEGF-D在浸润边缘的表达与NSCLC患者的淋巴结转移或淋巴道浸润显著相关，可能参与调节NSCLC的淋巴管生成和淋巴结转移。Anat Rec，293：802 - 812，2010. (C)2010 Wiley-Liss，Inc.
Vascular endothelial growth factor (VEGF)-C and VEGF-D induce lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3) and have been implicated in tumor spread to the lymphatic system. Lymph node dissemination critically determines clinical outcome and therapeutic options of patients with non-small cell lung cancer (NSCLC). However, the relationship of VEGF-C, VEGF-D, and lymph node metastasis in cancers, including NSCLC, is still controversial. To evaluate the relationship between lymphangiogenesis and lymph node metastasis, the expression of VEGF-C and VEGF-D in NSCLC tumors were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). QRT-PCR revealed that in marginal region VEGF-C and VEGF-D mRNA was significantly higher than in tumor center, and VEGF-D mRNA was also higher than that in peritumoral lung tissue Immunohistochemically, we observed the same heterogeneous expression of VEGF-C and VEGF-D proteins. The group with high expression of VEGF-C and VEGF-D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression. Furthermore, the group with high expression of VEGF-D in marginal region had a higher incidence of lymphatic invasion. The group with high peritumoral lymphatic vessel density (LVD) had higher expression of VEGF-C and VEGF-D mRNA compared with the group with low peritumoral LVD. Our studies suggested that the expression of VEGF-C and VEGF-D at invasive edge was significantly associated with lymph node metastasis or lymphatic invasion in patients with NSCLC and may be involved in regulation of lymphangiogenesis and lymph node metastasis in NSCLC. Anat Rec, 293:802-812, 2010. (C) 2010 Wiley-Liss, Inc.