Angiopoietin/Tie2 Enhances Vascular Radioresistance

血管生成素/Tie2 增强血管放射抵抗力

• 批准号: 7469410
• 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/7469410
• 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（申请人提供）：血管存活是血管发育的重要步骤，是维持血管正常功能的必要条件。迄今为止发现的一种分子机制是多肽生长因子激活内皮受体酪氨酸激酶（RTKs），它似乎在内皮细胞存活、迁移和血管发芽中起着重要作用。我们的实验室和其他研究证实了血管生成素/Tie2信号在内皮存活和血管稳定性中的关键作用。在肿瘤-宿主细胞相互作用中，包括血管生成素和血管内皮生长因子（VEGF）在内的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不平衡。因此，本研究将研究内皮细胞存活和放射抵抗。假设胶质瘤细胞和内皮细胞之间通过AngATie2信号通路的旁分泌调节介导内皮细胞存活并抵消辐射诱导的细胞死亡，有助于肿瘤血管的放射抵抗。