Spatial and Temporal Regulation of Angiogenesis

描述（由申请人提供） 血管生成是良性病变发展为肿瘤的关键步骤 威胁生命的疾病。该项目的中心主题是， 分子、细胞和组织形态学知识的整合 水平将导致空间和时间的详细了解 在新生儿、正常成人和肿瘤环境中调节血管生成。 子项目1将描述正常或肿瘤组织中的血管， 在各种细胞因子和抑制剂单独或联合存在的情况下形成 组合.该项目还将比较 来自新生儿、成人和VEGF-A过表达组织的内皮细胞。次级项目2 试图表征VEGF-A介导的信号传导途径下游的 KDR/Flk-1和Flt-1，并评估这些途径在正常和 肿瘤诱导的血管生成。次级项目3将界定规划和支助小组的作用， 正常皮肤的血管形成以及在炎症，癌变， 实验性肿瘤生长、转移和血管生成。次级项目4力求 表征作为受体的多蛋白复合物， 血小板反应蛋白-1（TSP-1）对内皮细胞的影响，并确定信号转导 介导TSP-1诱导的细胞凋亡的途径。核心A（行政 支持）将监督和协调科学，财政和监管 方案的操作。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）将准备和供应各种类型的 良好表征和标准化的内皮细胞。核心D（基因组学 支持）将进行基因分析研究，并将提供 生物信息学支持数据分析和挖掘。总的来说， 科学互动、合作以及试剂和专业知识的交流 本计划项目所提供的服务将有助于全面了解 血管生成的分子、细胞和形态学基础。

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.