Angiopoietin/Tie2 Enhances Vascular Radioresistance

血管生成素/Tie2 增强血管放射抵抗力

• 批准号: 7279812
• 负责人: Candice Shaifer
• 金额: $ 3.35万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-14 至 2009-08-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279812
• 关键词: Activation Date; Adult; Angiopoietins; Biological Assay; Blood Vessels; Blood flow; Brain Neoplasms; Cell Communication; Cell Death; Cell Survival; Cells; Cessation of life; Clinical; Coculture Techniques; Data; Development; Diagnosis; Disease regression; Dose; Drug resistance; Endothelial Cells; Endothelium; Fellowship; Glioblastoma; Glioma; Growth Factor; Individual; Lead; Ligands; Mediating; Modeling; Molecular; Names; Pathway interactions; Play; Radiation; Radiation therapy; Radio; Receptor Protein-Tyrosine Kinases; Regulation; Resistance; Role; Signal Pathway; Signal Transduction; TIE-2 Receptor; Testing; Time; Tube; Vascular Endothelial Growth Factors; Xenograft Model; improved; in vivo; migration; novel strategies; paracrine; polypeptide; prevent; receptor; response; tumor

DESCRIPTION (provided by applicant): Vascular survival is an integral step in vascular development and essential for maintaining proper vascular functions. One of the molecular mechanisms identified to date, activation of endothelial receptor tyrosine kinases (RTKs) by polypeptide growth factors, appears to play an important role in endothelial cell survival, migration and vessel sprouting. Studies from our lab and others confirm a critical role of angiopoietins/Tie2 signaling in endothelial survival and vascular stability. Within the tumor-host cell interaction there is an imbalance between survival signals including angiopoietins and vascular endothelial growth factor (VEGF) that favor vascular survival and drug resistance and, death signals induced by radiation which lead to endothelial cell death and tumor regression. Therefore, this proposal will examine endothelial cell survival and radio resistance. The hypothesis is that a paracrine regulation between glioma cells and endothelial cells via the AngATie2 signaling pathway mediates endothelial cell survival and counteracts radiation-induced cell death, contributing to radio resistance of tumor vasculature.

描述(由申请人提供)：血管存活是血管发育中不可或缺的一步，对维持适当的血管功能是必不可少的。多肽生长因子激活内皮细胞受体酪氨酸激酶(RTK)是目前已知的分子机制之一，它在内皮细胞的存活、迁移和血管萌发中起着重要作用。我们实验室和其他实验室的研究证实，血管生成素/Tie2信号在血管内皮细胞存活和血管稳定性中发挥着关键作用。在肿瘤-宿主细胞的相互作用中，血管生成素和血管内皮生长因子等有利于血管存活和耐药的生存信号与辐射诱导的导致内皮细胞死亡和肿瘤消退的死亡信号之间存在失衡。因此，这项建议将检查内皮细胞的存活率和辐射抗性。该假说认为，胶质瘤细胞和血管内皮细胞之间通过AngATie2信号通路的旁分泌调节，介导内皮细胞存活并对抗辐射诱导的细胞死亡，从而促进肿瘤血管的放射抵抗。