Spatial and Temporal Regulation of Angiogenesis

描述(由申请人提供) 血管生成是良性病变中肿瘤进展的关键步骤 威胁生命的疾病。这个项目的中心主题是 整合分子、细胞和组织形态的知识 水平将导致对空间和时间的详细理解 新生儿、正常成人和肿瘤环境中血管生成的调节。 子项目1将描述正常或肿瘤组织中的血管 在存在各种细胞因子和抑制物的情况下形成 组合。该项目还将比较 新生儿、成人血管内皮细胞和血管内皮生长因子-A高表达组织。子项目2 寻求表征血管内皮生长因子-A介导的信号通路下游 KDR/Flk-1和Flt-1，并评估这些通路在正常和 肿瘤诱导的血管生成。子项目3将确定PlGF在以下方面的作用 正常皮肤的血管化以及在炎症、癌变、 实验性肿瘤生长、转移和血管生成。子项目4寻求 描述作为受体的多蛋白复合体的特征 凝血酶敏感蛋白-1(TSP-1)对内皮细胞的作用及其信号转导机制 介导TSP-1诱导细胞凋亡的途径。核心A(行政管理 支持)将监督和协调科学、财政和监管 该程序的操作。核心B(形态支持)将提供专业知识 在电子显微镜、原位杂交和共聚焦显微镜中 程序。核心C(细胞生物学支持)将准备和提供各种类型 具有良好特性和标准化的内皮细胞。核心D(基因组学 支持)将执行基因图谱研究，并将提供 为数据分析和挖掘提供生物信息学支持。总而言之， 试剂和专门知识的科学互动、协作和交流 本计划提供的项目将使您全面了解 血管生成的分子、细胞和形态基础。

DESCRIPTION (provided by applicant) Angiogenesis is a key step in the progression of neoplasia from benign lesions to life-threatening disease. The central theme of this project is that the integration of knowledge from the molecular, cellular and tissue morphological levels will lead to a detailed understanding of the spatial and temporal regulation of angiogenesis in neonatal, normal adult and tumor settings. Subproject 1 will characterize blood vessels in normal or neoplastic tissue that form in the presence of various cytokines and inhibitors either alone or in combination. This project will also compare the gene expression of endothelium from neonatal, adult and VEGF-A overexpressing tissue. Subproject 2 seeks to characterize VEGF-A-mediated signaling pathways downstream of KDR/Flk-1 and Flt-1 and evaluate the role of these pathways in normal and tumor-induced angiogenesis. Subproject 3 will define the role of PlGF for vascularization of normal skin as well as during inflammation, carcinogenesis, experimental tumor growth, metastasis and angiogenesis. Subproject 4 seeks to characterize the multiprotein complex that functions as a receptor for thrombospondin-1 (TSP-1) on endothelial cells and determine the signaling pathways that mediate TSP-1-induced apoptosis. Core A (Administrative Support) will oversee and coordinate the scientific, fiscal and regulatory operations of the program. Core B (Morphology Support) will provide expertise in electron microscopy, in situ hybridization and confocal microscopy to the program. Core C (Cell Biology Support) will prepare and supply various types of well-characterized and standardized endothelial cells. Core D (Genomics Support) will perform the gene profiling studies and will provide bioinformatics support for data analysis and mining. Taken together, the scientific interactions, collaborations and exchange of reagents and expertise afforded by this Program Project will lead to a comprehensive understanding of the molecular, cellular and morphological basis of angiogenesis.