Angiopoietin/Tie2 Enhances Vascular Radioresistance

血管生成素/Tie2 增强血管放射抵抗力

• 批准号: 7158840
• 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/7158840
• 关键词: angiogenesis; angiopoietins; apoptosis; biological signal transduction; brain neoplasms; cell cell interaction; cell growth regulation; cell migration; cesium; gene induction /repression; genetic regulation; glioma; growth factor receptors; human tissue; immunocytochemistry; mixed tissue /cell culture; neoplasm /cancer; neoplasm /cancer blood supply; neoplastic growth; paracrine; predoctoral investigator; protein tyrosine kinase; radiation resistance; radionuclides; vascular endothelial growth factors; vascular endothelium

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的一个重要步骤，对于维持适当的血管功能至关重要。 迄今为止确定的分子机制之一，多肽生长因子激活内皮受体酪氨酸激酶（RTK），似乎在内皮细胞存活、迁移和血管出芽中起重要作用。 我们实验室和其他实验室的研究证实了血管生成素/Tie 2信号在内皮细胞存活和血管稳定性中的关键作用。 在肿瘤与宿主细胞的相互作用中，存活信号（包括有利于血管存活和耐药性的血管生成素和血管内皮生长因子（VEGF））与辐射诱导的死亡信号（导致内皮细胞死亡和肿瘤消退）之间存在不平衡。 因此，本提案将检查内皮细胞存活和放射抗性。 假设胶质瘤细胞和内皮细胞之间通过AngATie 2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，从而促进肿瘤血管的放射抗性。