MECHANISMS OF ANGIOGENESIS INHIBITION BY ANGIOSTATIN

血管抑制素抑制血管生成的机制

• 批准号: 6012635
• 负责人: MICHAEL W FANNON
• 金额: $ 3.17万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6012635
• 关键词: angiogenesis inhibitors; angiostatins; biological signal transduction; cardiovascular pharmacology; cell migration; cell proliferation; cofactor; drug receptors; pharmacokinetics; receptor binding; receptor expression; tissue /cell culture; western blottings

It has been shown that tumors, in order to grow and metastasize, must have access to a blood supply. Angiogenesis, or the growth of new blood vessels from existing ones, is the process by which tumor vasculature is formed. Traditional treatments of tumors, such as chemotherapy and radiation, create toxicity and drug resistance which preclude their long term use. A more effective strategy might be to target the growth of blood vessels to inhibit tumor growth rather than targeting the tumor cells themselves. Angiostatin, a fragment of plasminogen, has been shown to be a potent inhibitor of tumor growth and neovasculature in mice and additionally has shown no evidence of drug resistance or toxicity. Its mechanism of action, however, is not well understood. It is likely that angiostatin functions through receptor-mediated signaling but no receptor has yet been identified. This work will isolate the angiostatin receptor as well as potential angiostatin cofactors and characterize signaling molecules in its transduction pathway using traditional biochemical techniques. An understanding of the method by which angiostatin inhibits endothelial cell growth will aid in the design of other angiogenesis inhibitors.

已经表明，为了生长和转移，肿瘤必须获得血液供应。血管生成或现有血管的生长是形成肿瘤脉管系统的过程。肿瘤的传统疗法，例如化学疗法和放射线，会产生毒性和耐药性，从而排除了它们的长期使用。一个更有效的策略可能是靶向血管生长以抑制肿瘤生长，而不是针对肿瘤细胞本身。血管紧张素是纤溶酶原的片段，已被证明是小鼠肿瘤生长和新生血管的有效抑制剂，此外还没有显示出耐药性或毒性的证据。然而，它的作用机制尚不清楚。血管抑素可能通过受体介导的信号传导功能，但尚未鉴定出受体。这项工作将使用传统的生化技术隔离血管毒素受体以及潜在的血管毒素辅因子，并在其转导途径中表征信号分子。对Angiostatin抑制内皮细胞生长的方法的理解将有助于设计其他血管生成抑制剂。