Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines
Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines
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DOI：
10.1002/cncr.21145
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发表时间：
2005-07-15
期刊：
影响因子：
6.2
通讯作者：
Ellis, LM
中科院分区：
文献类型：
--
作者：
Wey, JS;Fan, F;Ellis, LM
背景血管内皮生长因子受体-1（VEGFR-1）是VEGF的三种受体酪氨酸激酶之一，VEGF是肿瘤血管生成的关键调节因子。尽管最初认为VEGFR仅在内皮细胞（EC）上表达，但最近的研究表明VEGFR-1在非EC类型上存在。作者假设VEGFR-1在胰腺癌细胞中存在并发挥功能，导致恶性表型。作者评估了VEGFR-1的表达。通过逆转录-聚合酶链反应、酶联免疫吸附试验和/或Western印迹分析，在11个胰腺癌细胞系中检测其及其配体。通过用VEGF-B（VEGFR-1的选择性配体）和/或特异性抗VEGFR-1抗体处理两种代表性细胞系，并评估对信号传导、迁移、侵袭和增殖的影响，评价VEGFR-1的功能。所有11种胰腺癌细胞系均表达VEGFR-1 mRNA和蛋白，以及VEGFR-1配体VEGF-A和VEGF-B。两种代表性细胞系（L3.6和Panc-1）显示VEGF-B诱导的丝裂原活化蛋白激酶信号传导。VEGFR-1中和抗体消除信号传导，证实配体效应是通过VEGFR-1介导的。发现VEGF-A或VEGF-B对VEGFR-1的刺激可促进两种细胞系的迁移。Panc-1细胞在VEGFR 1刺激后也表现出增强的基质胶侵袭。VEGFR-1依赖性迁移和侵袭被VEGFR-1中和抗体阻断。VEGFR-1的激活似乎并不增强细胞增殖。VEGFR-1似乎在胰腺癌细胞系中普遍表达，在胰腺癌细胞系中它诱导信号传导并促进迁移和侵袭。VEGF在肿瘤中的过表达可通过自分泌途径激活携带VEGFR-I的肿瘤细胞。靶向VEGF或其受体的药物可能通过抑制血管生成和肿瘤细胞功能对肿瘤生长具有双重抑制作用。(c)2005年美国癌症协会。
BACKGROUND. Vascular endothelial growth factor receptor-1 (VEGFR-1) is one of three receptor tyrosine kinases for VEGF, a key regulator of angiogenesis in cancer. Although VEGFRs initially were believed to be expressed exclusively on endothelial cells (ECs), recent studies have demonstrated the presence of VEGFR-1 on non-EC types. The authors hypothesized that VEGFR-1 is present and functional in pancreatic carcinoma cells, contributing to the malignant phenotype.METHODS. The authors assessed the expression of VEGFR-1. and its ligands in 11 pancreatic carcinoma cell lines by reverse-transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and/or Western blot analysis. The function of VEGFR-1 was evaluated by treating two representative cell lines with VEGF-B, a selective ligand for VEGFR-1, and/or a specific anti-VEGFR-1 antibody and assessing the effects on signaling, migration, invasion, and proliferation.RESULTS. All 11 pancreatic carcinoma cell lines expressed VEGFR-1 mRNA and protein, as well as the VEGFR-1 ligands VEGF-A and VEGF-B. Two representative cell lines (L3.6 and Panc-1) exhibited VEGF-B-induced mitogen-activated protein kinase signaling. A VEGFR-1 neutralizing antibody abrogated signaling, confirming that the ligand effect was mediated through VEGFR-1. VEGFR-1 stimulation by VEGF-A or VEGF-B was found to promote migration in both cell lines. Panc-1 cells also demonstrated enhanced Matrigel invasion after VEGFR1-stimulation. VEGFR-1-dependent migration and invasion were blocked by the VEGFR-1 neutralizing antibody. VEGFR-1 activation did not appear to enhance cell proliferation.CONCLUSIONS. VEGFR-1 appears to be expressed ubiquitously in pancreatic carcinoma cell lines, in which it induces signaling and promotes migration and invasion. Overexpression of VEGF in tumors may activate tumor cells bearing VEGFR-I via an autocrine pathway. Agents targeting VEGF or its receptors may have a dual inhibitory effect on tumor growth by suppressing both angingenesis and tumor cell function. (c) 2005 American Cancer Society.