Expression of VEGF receptors in cocultured neuroblastoma cells
Expression of VEGF receptors in cocultured neuroblastoma cells
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DOI：
10.1016/j.jss.2004.01.002
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发表时间：
2004-06-01
影响因子：
2.2
通讯作者：
Chen, MK
中科院分区：
文献类型：
--
作者：
Beierle, EA;Dai, W;Chen, MK
背景资料。血管内皮生长因子最为人所知的是它的血管生成特性。我们发现在与肝细胞共培养的神经母细胞瘤细胞中，血管内皮生长因子的表达增加。此外，我们先前已经证明，在外源血管内皮生长因子的培养下，神经母细胞瘤细胞中的血管内皮生长因子受体表达增加。因此，我们假设在共培养环境中生长的神经母细胞瘤细胞中血管内皮生长因子受体的表达将上调。使用两种神经母细胞瘤细胞系(IMR-32或SK-N-DZ)。这些细胞单独培养，并与肝细胞在共培养系统中培养。逆转录-聚合酶链式反应检测血管内皮生长因子及其受体KDR、Flt-1、Flt-4、NRP-1和NRP-2的表达。免疫印迹法检测Flt-4、NRP-1、NRP-2蛋白表达。在对照和共培养条件下，KDR和Flt-1受体在两种细胞系中均未检测到。在共培养的IMR-32细胞中，VEGF和Flt-4的表达显著增加，而NRP-1和NRP-2的表达没有变化。共同培养的SK-N-DZ细胞中，血管内皮生长因子及其受体没有变化。神经母细胞瘤细胞表达特定的血管内皮生长因子受体，这种受体在不同的细胞系中有不同的调节。这些发现表明，神经母细胞瘤的异质性可能会限制靶向血管内皮生长因子及其受体作为肿瘤唯一治疗方法的有效性，成功的治疗将取决于肿瘤的特定生物学特性。(C)2004 Elsevier Inc.保留所有权利。
Background. VEGF is best known for its angiogenic properties. We have found that VEGF expression is increased in neuroblastoma cells cocultured with hepatocytes. In addition, we have previously shown that neuroblastoma cells cultured with exogenous VEGF have an increase in the expression of VEGF receptors. Therefore, we hypothesized that the expression of VEGF receptors would be up-regulated in neuroblastoma cells grown in the coculture environment.Materials and methods. Two neuroblastoma cell lines (IMR-32 or SK-N-DZ) are used. These cells are cultured alone and in a coculture system with hepatocytes. Message for VEGF and the VEGF receptors KDR, flt-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2) are measured with RT-PCR. Flt-4, NRP-1, and NRP-2 protein expression is measured with Western blot.Results. The receptors KDR and flt-1 are not detected in either cell line in either control or coculture conditions. Message for VEGF and flt-4 is significantly increased in the cocultured IMR-32 cells, while that for NRP-1 and NRP-2 is unchanged in these cells. VEGF and its receptors are unchanged in cocultured SK-N-DZ cells.Conclusions. Neuroblastoma cells express specific VEGF receptors that are differentially regulated in the different cell lines. These findings suggest that the heterogeneity of neuroblastomas may limit the utility of targeting VEGF and its receptors as sole treatments for the tumor, and that successful therapies will be dependent upon the specific biology of the tumor. (C) 2004 Elsevier Inc. All rights reserved.