...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular Cancer >Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion
【24h】

Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

机译：ADAMTS-1在人乳腺肿瘤中的表达降低会刺激迁移和侵袭

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background ADAMTS -1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS -1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS -1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS -1 mRNA expression but lower levels of ADAMTS -1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS -1 knockdown in breast cancer cells in vitro . MDA-MB-231 cells with depleted ADAMTS -1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS -1 may be related to VEGF , a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS -1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells ( HUVEC ) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS -1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS -1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS -1 expression was decreased in human breast tumors, and ADAMTS -1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro . Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS -1 in breast cancer cells.
机译：背景技术ADAMTS -1（具有血小板反应蛋白基序的整合素和金属蛋白酶）是金属蛋白酶ADAMTS家族的成员。在这里，我们使用qPCR，免疫组化和免疫印迹分析研究了正常和赘生组织中ADAMTS -1的mRNA和蛋白水平，并探讨了ADAMTS -1在调节乳腺癌细胞系中迁移，侵袭和侵袭伪足形成中的作用。结果在一系列原发性乳腺肿瘤中，我们观察到与正常组织相比，人乳腺癌中ADAMTS -1 mRNA表达水平可变，但ADAMTS -1蛋白表达水平较低，在高恶性肿瘤病例中观察到显着下降（三倍） -雌激素，孕酮和Her-2阴性）。这一结果促使我们分析ADAMTS -1基因敲除对乳腺癌细胞的影响。具有减少的ADAMTS -1表达的MDA-MB-231细胞表现出增加的迁移，侵袭和侵袭伪足形成。 ADAMTS -1作用的潜在调节机制可能与VEGF有关，VEGF是一种参与迁移和侵袭的生长因子。具有减少的ADAMTS -1的MDA-MB-231细胞在能够诱导人内皮细胞（HUVEC）肾小管生成的条件培养基中显示出增加的VEGF浓度。此外，与MCF7细胞相比，MDA-MB-231细胞中VEGF受体（VEGFR2）的表达增加。为了进一步确定ADAMTS -1与调节VEGF的乳腺癌细胞之间的关系，将ADAMTS -1表达降低的MDA-MB-231细胞用抗VEGF的功能阻断抗体进行预处理，然后在迁移和侵袭实验中进行测试;两者都被部分救出至控制水平。结论ADAMTS -1在人乳腺肿瘤中的表达降低，而ADAMTS -1的敲低刺激了乳腺癌细胞的迁移，侵袭和伪足形成。因此，该系列实验表明VEGF参与了乳腺癌细胞中ADAMTS -1介导的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号