首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner
【24h】

Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner

机译:平衡血管生成调节因子以特定阶段的方式控制癌症进展和存活率

获取原文
获取原文并翻译 | 示例
           

摘要

Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, adminis tration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, corre lating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis.
机译:尽管促血管生成因子在致癌作用中的作用已得到充分确立,但内源性血管生成抑制剂(EAI)的作用仍有待充分阐述。我们研究了三种EAI在新生肿瘤发生过程中的作用,以进一步检验血管生成平衡假说,这表明,除了公认的原理外,肿瘤微环境中血管的发育还可以由血管生成负调节剂的净损失来控制。上调血管生成诱导剂。在胰腺神经内分泌癌的小鼠模型中,对内皮抑素,血小板反应蛋白-1和肿瘤抑素肽的管理以及它们的基因缺失显示出与血管内皮表达相关的肿瘤阶段特异性作用于血管生成,肿瘤进展和生存他们的受体。缺乏p53抑癌基因的小鼠中的tumstatin和thrombospondin-1的缺失会导致血管生成性淋巴瘤的发病率增加和潜伏期缩短,从而降低总生存期。结果表明,EAIs是调节肿瘤血管生成的平衡机制的一部分,是肿瘤发生的固有微环境障碍。

著录项

  • 来源
  • 作者单位

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Diabetes and Comprehensive Cancer Centers, University of California, San Francisco, CA 94143;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Department of Medical Biochemistry and Microbiology, Uppsala University,75105 Uppsala, Sweden,Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139;

    Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan;

    Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan;

    Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;

    Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139;

    Diabetes and Comprehensive Cancer Centers, University of California, San Francisco, CA 94143;

    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215,Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215,Harvard-MIT Division of Health Sciences and Technology,Boston, MA 02215;

  • 收录信息 美国《科学引文索引》(SCI);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
  • 关键词

    integrins; cell biology;

    机译:整合素;细胞生物学;

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