S100A4 antisense oligodeoxynucteotide suppresses invasive potential of neuroblastoma cells
S100A4 antisense oligodeoxynucteotide suppresses invasive potential of neuroblastoma cells
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DOI：
10.1016/j.jpedsurg.2005.01.007
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发表时间：
2005-04-01
影响因子：
2.4
通讯作者：
Zhang, XF
中科院分区：
文献类型：
--
作者：
Gao, XN;Tang, SQ;Zhang, XF
背景：S100 A4基因产物参与肿瘤的侵袭和转移。神经母细胞瘤患儿的总体生存率仍然很低，因为在诊断时疾病已扩散。本研究旨在探讨S100 A4在神经母细胞瘤侵袭和转移中的作用及其机制。方法：采用脂质体介导法，将针对S100 A4基因的20-mer硫代反义寡核苷酸（asODN）转染人神经母细胞瘤细胞系LA-N-6。逆转录聚合酶链反应检测S100 A4和MMP-2 mRNA的表达。结果：经asODN处理的LA-N-6细胞S100 A4 mRNA和MMP-2 mRNA表达水平较未处理的细胞分别降低35.6%和25.5%。经asODN处理的LA-N-6细胞迁移和侵袭的数量均显著低于未处理组（分别为9.33 +/- 4.73 vs 20.67 +/- 2.89和2.33 +/- 1.15 vs 9.00 +/- 2.65;均P = 0.03）。S100 A4 asODN可显著降低神经母细胞瘤细胞S100 A4 mRNA的表达水平，降低细胞的运动能力和侵袭能力，同时降低MMP-2 mRNA的表达水平。因此，S100 A4可能通过刺激肿瘤细胞的运动性以及影响MMP-2的表达来影响神经母细胞瘤细胞的侵袭和转移。(c)2005年爱思唯尔公司All rights reserved.
Background: S100A4 gene product has been implicated in tumor invasion and metastasis. The overall survival rate of children with neuroblastoma remains poor because of disease dissemination at the time of diagnosis. The purpose of this study was to investigate the effect and mechanism of S100A4 on invasion and metastasis of neuroblastoma.Methods: A 20-mer phosphorothioate antisense oligodeoxynucleotide (asODN) targeted against the S100A4 mRNA was transfected into the human neuroblastoma cell line LA-N-6 by Lipofectamine 2000. The expressions of S100A4 and MMP-2 mRNAs were quantified by the reverse transcription polymerase chain reaction. The capability of migration and invasion of LA-N-6 cells were evaluated by the transwell chamber assay.Results: The S100A4 mRNA and the MMP-2 mRNA levels in asODN-treated cells were decreased by 35.6% and 25.5%, respectively, compared with those in nontreated cells. The numbers of migrating and invading LA-N-6 cells were both significantly lower in the asODN-treated groups than those in the nontreated groups (9.33 +/- 4.73 vs 20.67 +/- 2.89 and 2.33 +/- 1.15 vs 9.00 +/- 2.65, respectively; both P =.03).Conclusions: The S100A4 asODN significantly reduced the S100A4 mRNA levels and the motility and invasive ability of neuroblastoma cells, with concomitant decrease of the MMP-2 mRNA levels. Thus, S100A4 may exert its effect on invasion and metastasis of neuroblastoma cells by stimulating the motility of tumor cells as well as influencing the expression of MMP-2. (c) 2005 Elsevier Inc. All rights reserved.