• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Expression of MT1-MMP in Head and Neck Squamous Cell Carcinomas (HNSCCs) and Endothelial Cells is Regulated by Hypoxia and Semaphorin 4D (Sema4D).
【24h】

Expression of MT1-MMP in Head and Neck Squamous Cell Carcinomas (HNSCCs) and Endothelial Cells is Regulated by Hypoxia and Semaphorin 4D (Sema4D).

机译：低氧和Semaphorin 4D（Sema4D）调节头颈部鳞状细胞癌（HNSCC）和内皮细胞中MT1-MMP的表达。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Membrane type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane protein that is important in tumor growth, migration, and invasion. It has the ability to degrade ECM, non-matrix proteins such as CD44 and integrin, and activate MMP2. Semaphorin 4D (Sema4D), a membrane-bound semaphorin, is highly expressed in malignancies such as head and neck squamous cell carcinoma (HNSCC) and is known to be pro-angiogenic, promoting the growth of blood vessels into a developing tumor by acting as a chemoattractant when bound to its receptor, Plexin-B1 (PB1), on endothelial cells. Our central hypothesis is that tumor hypoxia causes an increase in Sema4D, which acts in an autocrine and paracrine manner on tumor cells to induce the overexpression of MT1-MMP, which, in turn, cleaves Sema4D and increases availability to the tumor microenvironment to promote tumor-induced angiogenesis and invasion. Using immunoblots and flow cytometry, we demonstrate that MT1-MMP increases in HNSCC cells in a Sema4D and Plexin-B1-dependent manner in hypoxia. Also, we show that RhoA and NF-kappaB (downstream effectors of Plexin-B1) are important in the regulation of cell surface MT1-MMP expression under hypoxic conditions. Consequently, tumor-induced invasion and angiogenesis are enhanced. Soluble Sema4D diffuses out from the tumor and acts as a chemoattractant for endothelial cells, which also upregulate MT1-MMP on their surface to facilitate migration through the extracellular matrix. We conclude that Sema4D controls its own availability and, therefore, its own pro-angiogenic potential through autocrine/paracrine regulation of MT1-MMP.
机译：膜1型基质金属蛋白酶（MT1-MMP）是不可或缺的膜蛋白，在肿瘤的生长，迁移和侵袭中很重要。它具有降解ECM，非基质蛋白（例如CD44和整联蛋白）并激活MMP2的能力。 Semaphorin 4D（Sema4D）是一种膜结合型Semaphorin，在诸如头颈鳞状细胞癌（HNSCC）的恶性肿瘤中高表达，并且已知具有促血管生成作用，通过充当以下分子而促进血管生长为正在发展的肿瘤与内皮细胞上的受体Plexin-B1（PB1）结合时产生的化学吸引剂。我们的主要假设是，肿瘤缺氧会导致Sema4D增加，Sema4D以自分泌和旁分泌的方式作用于肿瘤细胞，从而诱导MT1-MMP的过表达，进而裂解Sema4D并增加肿瘤微环境的利用率，从而促进肿瘤发展。诱导的血管生成和侵袭。使用免疫印迹和流式细胞仪，我们证明在缺氧状态下，HNSCC细胞中MT1-MMP以Sema4D和Plexin-B1依赖性方式增加。此外，我们显示RhoA和NF-κB（Plexin-B1的下游效应子）在缺氧条件下对细胞表面MT1-MMP表达的调节中很重要。因此，增强了肿瘤诱导的侵袭和血管生成。可溶性Sema4D从肿瘤扩散出去，并充当内皮细胞的化学吸引剂，内皮细胞也上调其表面的MT1-MMP从而促进通过细胞外基质的迁移。我们得出的结论是，Sema4D通过MT1-MMP的自分泌/旁分泌调节来控制自身的可用性，并因此控制自身的促血管生成潜力。

著录项

  • 作者

    Bugshan, Amr.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Oncology.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 84 p.
  • 总页数 84
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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