Tumor-derived vascular endothelial growth factor (VEGF)-A facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway
Tumor-derived vascular endothelial growth factor (VEGF)-A facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway
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DOI：
10.3892/ijo.2011.1138
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发表时间：
2011-11-01
影响因子：
5.2
通讯作者：
Han, Mingyong
中科院分区：
文献类型：
--
作者：
Liu, Wenbo;Xu, Jiying;Han, Mingyong
血管内皮生长因子（VEGF）及其受体参与肿瘤的发生、侵袭和肿瘤血管生成，但VEGF促进肿瘤转移的机制尚不清楚。在这项研究中，我们发现，在癌症患者中，VEGF的高表达与转移相关，抗VEGF治疗（贝伐单抗）对肿瘤转移具有临床效果。将两种具有不同VEGF表达的人肺癌细胞系（A549和SPCA 1细胞）通过SCID小鼠的侧尾静脉静脉注射，并建立小鼠模型。通过微血管密度、免疫组化和整体包埋染色研究VEGF表达与肿瘤转移的关系。在处死时，在高VEGF表达的A549细胞系组中，诱导的肿瘤在尺寸上明显更大，并且在肺组织中发现多个转移病灶。将两种特异性中和性抗小鼠VEGFR I和VEGFR 2抗体给予荷瘤小鼠;抗VEGFR 1而非抗VEGFR 2治疗对VEGF诱导的肿瘤转移产生抑制作用。这些发现表明VEGF-VEGFR 1信号通路在肿瘤转移中起着至关重要的作用，阻断VEGF-VEGFR 1诱导的转移可能为预防和治疗肿瘤转移提供新的途径。
Vascular endothelial growth factor (VEGF) and its receptors are involved in carcinogenesis, invasion and tumor angiogenesis, but the underlying mechanism by which VEGF promotes tumor metastasis is poorly understood. In this study, we show that in cancer patients high expression of VEGF is correlated with metastasis, and anti-VEGF treatment (bevacizumab) has clinical effects on tumor metastasis. Two human lung carcinoma cell lines (A549 and SPCA1 cells) with distinct VEGF expression were injected intravenously through the lateral tail vein of SCID mice and a murine model was developed. We investigated the association between the expression of VEGF and tumor metastasis by microvessel density, immunohistochemistry and whole mount staining. At sacrifice, in the high VEGF expression A549 cell line group, the induced tumor was distinctively larger in size and multiple metastatic lesions were found in lung tissues. Two specific neutralizing anti-mouse VEGFR I and VEGFR2 antibodies were administered to the tumor-bearing mice; anti-VEGFR1, but not anti-VEGFR2 treatment produced inhibitive effects on VEGF-induced tumor metastasis. These findings demonstrate that the VEGF-VEGFR1 signaling pathway is crucial for tumor metastasis and the blockade of VEGF-VEGFR1-induced metastasis may provide a novel approach for the prevention and treatment of tumor metastasis.