Induction of lymphangiogenesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma
Induction of lymphangiogenesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma
复制标题
DOI：
10.1016/j.oraloncology.2012.02.003
复制
发表时间：
2012-08-01
期刊：
影响因子：
4.8
通讯作者：
Yoshizaki, Tomokazu
中科院分区：
文献类型：
--
作者：
Wakisaka, Naohiro;Hirota, Kyoko;Yoshizaki, Tomokazu
通过对人类癌症的研究，淋巴系统对肿瘤转移的贡献越来越受到重视。由于鼻咽癌的生物学特性取决于其淋巴结状态，晚期淋巴结状态的患者表现出更高的预后不良倾向。在此，我们研究了淋巴管生成在鼻咽癌淋巴扩散中的作用。我们还评估了血管内皮生长因子（VEGF）-C/VEGF受体3（VEGFR 3）信号通路在鼻咽癌淋巴管生成中的作用。此外，我们测试了EB病毒（EBV）-潜伏膜蛋白（LMP）1是否诱导VEGF-C。采用免疫组化方法检测41例鼻咽癌组织中VEGF-C及其受体、VEGFR 3和LMP 1蛋白的表达，并以antipodoplanin标记淋巴管计数（LVC）。采用Westernblotting和酶联免疫吸附试验检测LMP 1对VEGF-C的体外诱导作用。LVC和VEGF-C表达在有晚期区域淋巴结转移的病例中（N2，3）显著高于无淋巴结转移或淋巴结转移有限的病例（N 0，1）（分别为p = 0.0380和p = 0.0109）。在VEGF-C/VEGFR 3阳性病例中，与VEGF-C/VEGFR 3阴性病例相比，LVC显著增加（p = 0.0007）。然而，LMP 1表达与LVC和VEGF-C表达评分无显著相关性（分别为p = 0.1210和p = 0.1324）。在体外未检测到LMP 1诱导VEGF-C蛋白的表达。这些结果表明VEGF-C/VEGFR 3轴参与了导致NPC淋巴扩散的淋巴管生成的诱导。但EBV-LMP 1与该机制无关。(c)2011爱思唯尔有限公司保留所有权利。
The contribution of the lymphatic system to tumor metastasis is being increasingly appreciated through studies of human cancers. As the biological of nasopharyngeal carcinoma (NPC) depends on its nodal status, patients with advanced nodal status show a higher tendency toward a poor outcome. Here, we examined the role of lymphangiogenesis on lymphatic spread of NPC. We also evaluated the involvement of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR3) signaling pathway on lymphangiogenesis in NPC. Furthermore, we tested whether Epstein-Barr virus (EBV)-latent membrane protein (LMP) 1 induces VEGF-C. Forty-one patients with NPC were evaluated for expressions of VEGF-C and its receptor, VEGFR3, and LMP1 proteins and lymphatic vessel counts (LVC) highlighted by antipodoplanin employing immunohistochemistry. The VEGF-C induction by LMP1 was then tested with Western blotting and enzyme-linked immunosorbent assay in vitro. The LVC and VEGF-C expression were significantly higher in cases with advanced regional lymph node metastasis (N2,3) than those with no or limited lymph node involvement (N0,1) (p = 0.0380 and p = 0.0109, respectively). In VEGF-C/VEGFR3-positive cases, the LVC were significantly increased compared with VEGF-C/VEGFR3-negative cases (p = 0.0007). However, LMP1 expression did not show significant associations with LVC and VEGF-C-expression scores (p = 0.1210 and p = 0.1324, respectively). Induction of VEGF-C protein by LMP1 was not detected in vitro. These results suggest the involvement of the VEGF-C/VEGFR3 axis in the induction of lymphangiogenesis which results in lymphatic spread of NPC. However, EBV-LMP1 was not associated with the mechanism. (c) 2011 Elsevier Ltd. All rights reserved.