• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Signalling silenced
【24h】

Signalling silenced

机译：信号静音

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

Tumours and inflamed tissues cannot grow without blood vessels to supply them with oxygen. So interfering with the formation of new blood vessels has been proposed as an attractive means of combating both cancer and inflammation. One class of proteins that stimulates bloodvessel formation (angiogenesis) is the matrix metalloproteinases (MMPs), which are kept in check by molecules called tissue inhibitors of MMPs (TIMPs). TIMPs suppress both angiogenesis and tumour growth, suggesting that synthetic compounds mimicking the MMP-inhibiting effects of these proteins might prove useful in treating cancer. But such efforts have generally been disappointing. This could be explained by the fact that TIMPs also have other effects, and, writing in Cell, Seo et al. reveal a further, surprising function for one key TIMP. They show that it prevents angiogenesis by blocking a cellular signalling pathway, and that this ability has nothing to do with its MMP-inhibiting capacity. The idea that blocking angiogenesis might prove beneficial for treating cancer is supported by recent evidence that an inhibitor of a prime angiogenic molecule―vascular endothelial growth factor (VEGF)―prolongs survival of cancer patients (see ref. 6 for a comment on this finding). One mechanism by which VEGF promotes angiogenesis is by stimulating protein-degrading (proteolytic) enzymes, including MMPs. When first discovered, MMPs were thought to work mainly by breaking through the dense thicket of fibres that surrounds cells, thereby allowing cancer cells and blood vessels to invade surrounding tissues. The TIMPs, which inhibit the proteolytic activity of MMPs, suppress the migration of endothelial cells (which line blood vessels) and angiogenesis. Together, these findings provided the rationale for treating cancer with synthetic compounds that, like TIMPs, block MMP activity―a formidable effort in which the pharmaceutical industry has invested at least a billion dollars over the past 20 years.
机译：没有血管向它们提供氧气，肿瘤和发炎的组织就无法生长。因此，已经提出了干扰新血管的形成作为对抗癌症和炎症的有吸引力的手段。刺激血管形成（血管生成）的一类蛋白质是基质金属蛋白酶（MMP），其被称为MMPs组织抑制剂（TIMPs）的分子所控制。 TIMPs抑制血管生成和肿瘤的生长，表明模仿这些蛋白的MMP抑制作用的合成化合物可能被证明可用于治疗癌症。但是这样的努力通常令人失望。 TIMPs也具有其他作用，Seo等人在Cell中写道。揭示了一个关键TIMP的另一令人惊讶的功能。他们表明，它通过阻断细胞信号通路来阻止血管生成，并且这种能力与其MMP抑制能力无关。最近的证据表明，阻断血管生成可能被证明对治疗癌症有益，这一观点得到了最新证据的支持，即血管新生分子抑制剂血管内皮生长因子（VEGF）可以延长癌症患者的生存期（有关此发现的评论，请参见参考文献6）。 。 VEGF促进血管生成的一种机制是通过刺激包括MMPs在内的蛋白质降解（蛋白水解）酶。最早发现时，人们认为MMP主要是通过突破细胞周围纤维的致密丛而起作用的，从而使癌细胞和血管侵入周围组织。 TIMP抑制MMP的蛋白水解活性，抑制内皮细胞（在血管内）的迁移和血管生成。这些发现共同为使用合成化合物治疗癌症提供了理论依据，这些合成化合物可以阻止MMP活性，而TIMPs可以阻止MMP的活性，这是制药行业在过去20年中投入的至少十亿美元。

著录项

  • 来源
    《Nature》 |2003年第6954期|p.139-141|共3页
  • 作者

    Edward M Conway; Peter Carmeliet;

  • 作者单位

    Centre for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, B-300 Leuven, Belgium;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 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