Inhibition of Angiogenesis by TSP-1 & TSP-1 Peptides

TSP-1 抑制血管生成

• 批准号: 7105031
• 负责人: TANYA A REGE
• 金额: $ 2.85万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-06 至 2007-06-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105031
• 关键词: angiogenesis; angiogenesis inhibitors; antineoplastics; apoptosis; astrocytoma; athymic mouse; biological signal transduction; brain circulation; cell growth regulation; cell proliferation; cysteine endopeptidases; enzyme activity; flow cytometry; genetically modified animals; laboratory mouse; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; neoplastic growth; nonhuman therapy evaluation; predoctoral investigator; protein structure function; thrombospondins; vascular endothelium; western blottings

DESCRIPTION (provided by applicant): Angiogenesis is necessary for malignant tumor growth and invasion. Current data from other investigators indicate that intact thrombospondin-1 (TSP-1) and peptides derived from the type 1 repeat domain of TSP-1 can inhibit angiogenesis of non-brain microvascular endothelial cells by a mechanism thought to be apoptotic in nature, suggesting the induction of microvascular endothelial cell death is the mechanism by which TSP-1, as well as peptides derived from the type 1 repeat domain, inhibit angiogenesis. Thus, TSP-1 and type 1 repeat peptides will likely inhibit angiogenesis of brain microvascular endothelial cells by inducing apoptosis. This proposal will define by biochemical methods the apoptotic signaling cascade induced by TSP-1 and type 1 repeat peptides in brain microvascular endothelial cells in vitro, confirm and extend these observations using brain microvascular endothelial cells isolated from mice deficient in specific apoptotic signaling molecules, and test the therapeutic efficacy of type 1 repeat peptides in inhibiting angiogenesis and tumor growth in an intracerebral xenograft model of malignant astrocytoma.

描述（由申请人提供）： 血管生成对于恶性肿瘤的生长和侵袭是必要的。来自其他研究者的当前数据表明，从TSP-1的1型重复结构域中得出的完整血栓形成蛋白-1（TSP-1）和肽可以通过一种本质上的机制抑制非脑部微血管内皮细胞的血管生成，该机制本质上是凋亡的，表明诱导了微血管内皮细胞死亡的诱导源是SPS-1，以及该机制，以及该机构的类型，以及The Sps-1的机制，以及THESSS SPS，以及THESSSS SPS-1的pept pests and Sps-1 pept pept pepts and Sps-1抑制血管生成。因此，TSP-1和1型重复肽可能会通过诱导凋亡来抑制脑微血管内皮细胞的血管生成。该提议将通过生化方法定义脑微血管内皮细胞中TSP-1和1型重复肽诱导的凋亡信号传导级联，并使用脑部微血管内皮细胞在体外确认并扩展了这些观察，并扩展了这些观察，从而从小鼠中分离出了在特定的Apoptotic信号分子和验证型的典型拟合性拟型拟型拟南芥中，并延伸恶性星形细胞瘤的脑内异种移植模型的生长。