Role and Utility of Annexins in Endothelium of Solid Tum

该项目的主要目的是了解肿瘤微环境对内皮功能影响的分子机制，以及特异性肿瘤诱导的内皮细胞蛋白对肿瘤生长、进展和血管生成的影响。这些基本信息对于开发新的诊断和治疗策略至关重要，这些策略可能有助于改善实体肿瘤的早期发现和治疗。我们将集中精力研究新的肿瘤诱导的内皮细胞和小窝靶点，一种AnnAl相关蛋白，通过我们对肿瘤腔内皮细胞的蛋白质组学分析鉴定。 膜。我们将定义这种蛋白质的特定性质和功能，并使用针对这种新靶蛋白的特异性抗体组来评估实体瘤及其内皮细胞中的表达和功能。为此，我们将致力于实现以下具体目标：1.确定肿瘤细胞和组织宿主环境（包括特异性血管生成因子）对其在小窝中的表达、移位和外化的作用。2.研究其在肿瘤内皮细胞中的表达对内皮细胞功能、实体瘤生长和血管生成的作用。我们将使用各种大鼠和小鼠肿瘤模型系统以及多种生物化学和显微镜方法来检查体内和细胞中的 培养小窝特异性表达的功能。例如，将评估阻断可能的蛋白质功能的裸抗体的潜在抗肿瘤作用。有了这些信息，我们计划开发改善实体瘤检测和分期的方法，并制定更有效、毒性更低的抗癌治疗新策略。

The broad focus of this project is to understand the molecular mechanisms underlying the effects of the tumor microenviroment on endothelial function and the effects of specific tumor-induced endothelial cell proteins on tumor growth, progression and angiogenesis. Such basic information is essential to develop new diagnostic and therapeutic strategies that may prove useful in improving the early detection and treatment of solid t umors. W e w ill focus p rimarily one haracterizing our new tumor-induced, endothelial and caveolar target, an AnnAl related protein, identified through our proteomic analysis of tumor luminal endothelial cell membranes. We will define the specific nature and function of this protein as well as use our panel of specific antibodies to this new target protein to evaluate expression and function in the context of solid tumors and its endothelium. To this end, we will address the following specific aims: 1. To determine the role of the tumor cell and tissue host environment, including specific angiogenic factors, on its expression, translocation, and externalization in caveolae. 2. To investigate the role of its expression by the tumor endothelium on endothelial cell function, solid tumor growth, and angiogenesis. We will use various rat and mouse tumor model systems as well as multiple biochemical and microscopic methodologies to examine in vivo and in cell culture the function of specific expression in caveolae. For instance, the potential anti-tumor effects of naked antibodies blocking possible protein function will be assessed. With this information, we plan to develop the means to improve the detection and staging of solid tumors as well as elaborate novel strategies for more effective and less toxic anti-cancer treatments.