VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma.
VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma.
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VEGF通过调节鼻咽癌EMT和MMPs促进迁移和侵袭
DOI：
10.7150/jca.46429
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发表时间：
2020
影响因子：
3.9
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Chen L;Lin G;Chen K;Liang R;Wan F;Zhang C;Tian G;Zhu X
背景：血管内皮生长因子（VEGF）是一种重要的促血管生成因子。越来越多的资料表明VEGF参与肿瘤转移。然而，VEGF调节鼻咽癌（NPC）转移的机制在很大程度上是未知的。本研究旨在探讨VEGF在鼻咽癌转移中的生物学作用及其机制。研究方法：我们使用蛋白质印迹和qPCR检测鼻咽癌细胞和永生化鼻咽上皮细胞系NP 69之间VEGF表达的差异。通过创伤愈合实验、transwell实验和动物实验进一步验证VEGF在鼻咽癌细胞侵袭和迁移中的作用。采用免疫荧光法和蛋白质印迹法分析上皮间质转化（EMT）和基质金属蛋白酶（MMP）家族的蛋白水平。采用酶联免疫吸附试验（ELISA）和transwell法检测VEGF是否以自分泌方式促进鼻咽癌细胞的侵袭和迁移。蛋白质印迹法用于检测自分泌VEGF-VEGFR 2信号传导如何调节EMT和MMPs。结果如下：我们观察到鼻咽癌细胞中的VEGF水平高于NP 69细胞，并确定了高VEGF水平与肿瘤侵袭和迁移之间的关联。VEGF介导的EMT标志物MMP 2和MMP 9的增加促进NPC细胞的侵袭和迁移。此外，NPC细胞分泌VEGF以促进细胞侵袭、迁移和血管生成。自分泌VEGF-VEGFR 2信号在指定时间增加ERK 1/2磷酸化，促进EMT过程和MMPs。结论：VEGF通过自分泌方式调控EMT标志物和MMPs，从而控制鼻咽癌细胞的转移。
Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. Accumulating data have indicated that VEGF is involved in tumour metastasis. However, the mechanism through which VEGF regulates nasopharyngeal carcinoma (NPC) metastasis is largely unknown. This study aimed to examine the biological function of VEGF in NPC metastasis and its underlying mechanism. Methods: We used western blotting and qPCR to examine the difference in VEGF expression between NPC cells and the immortalized nasopharyngeal epithelial cell line NP69. Wound healing assays, transwell assays and animal experiments were used to further verify the role of VEGF in the invasion and migration of NPC cells. The protein levels of the epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family were analysed by immunofluorescence (IF) and western blotting. Enzyme-linked immunosorbent assay (ELISA) and transwell assays were used to determine whether VEGF enhanced the invasion and migration of NPC cells in an autocrine manner. Western blotting was used to examine how autocrine VEGF-VEGFR2 signalling regulated EMT and MMPs. Results: We observed higher levels of VEGF in NPC cells than that in NP69 cells and identified an association between high VEGF levels and tumour invasion and migration. Mechanistically, the VEGF-mediated increase in EMT markers, MMP2 and MMP9 promoted NPC cell invasion and migration. Additionally, NPC cells secreted VEGF to promote cell invasion, migration and angiogenesis. Autocrine VEGF-VEGFR2 signalling increased ERK1/2 phosphorylation, promoted EMT process and MMPs at the indicated times. Conclusion: This study revealed that VEGF plays a role in controlling NPC cell metastasis by regulating EMT markers and MMPs in an autocrine manner.
影响因子：
3.8
作者：
Oh SY;Kwon HC;Kim SH;Lee S;Lee JH;Hwang JA;Hong SH;Graves CA;Camphausen K;Kim HJ;Lee YS
通讯作者：
Lee YS