Role and Utility of Annexins in Endothelium of Solid Tum

该项目的主要重点是了解肿瘤微环境对内皮功能影响的分子机制，以及特定的肿瘤诱导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，这些策略可能被证明有助于改善实体肿瘤的早期发现和治疗。通过对肿瘤腔内皮细胞的蛋白质组学分析，我们将着重描述我们的新的肿瘤诱导的内皮和凹陷靶点，这是一种与年度相关的蛋白。 膜。我们将定义这种蛋白的特殊性质和功能，并使用我们的一组针对这种新的靶蛋白的特异性抗体来评估在实体瘤及其内皮的背景下的表达和功能。为此，我们将解决以下具体目标：1.确定肿瘤细胞和组织宿主环境，包括特定的血管生成因子，对其在小窝中的表达、转位和外化的作用。2.探讨其在肿瘤内皮细胞表达对内皮细胞功能、实体瘤生长及血管生成的影响。我们将使用各种大鼠和小鼠肿瘤模型系统以及多种生化和显微方法来检测体内和细胞内 培养小窝中特异表达的功能。例如，将评估阻断可能的蛋白质功能的裸体抗体的潜在抗肿瘤效果。有了这些信息，我们计划开发改进实体肿瘤的检测和分期的方法，并为更有效和毒性更低的抗癌治疗制定新的策略。

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.