MAGIC ROUNDABOUT (MRB), A TUMOR ENDOTHELIAL MARKER

描述(由申请人提供)：基于分子的新疗法的开发和应用是至关重要的。发展这种合理的治疗方法的关键在于识别合适的分子标志物。尽管肿瘤的进展依赖于血管生成，但关于正常血管内皮细胞和肿瘤血管内皮细胞之间的特征差异，仍然存在一些基本问题。因此，需要新的标记物来区分正常和肿瘤血管内皮细胞。重要的是，这些标记物可能为抗血管治疗提供潜在的治疗靶点。 魔术环行蛋白是一个环行交叉口受体家族成员，具有内皮细胞限制性表达。我们的初步数据显示，MRB在肿瘤内皮细胞中高表达，而在正常内皮细胞中明显减少或缺失。因此，在特定的目标1中，我们建议利用MRB的肿瘤内皮限制性表达来验证MRB表达可用于体内肿瘤内皮分子成像的假设。预计投资我们的资源开发MRB作为肿瘤血管成像靶点可能提供一种工具来监测各种抗血管生成/血管治疗的疗效。在特定的目标2中，我们建议从原发肾细胞癌(RCC)中分离出其他候选的肿瘤内皮标志物(TEM)，并评估它们在RCC转移部位的表达。部分TEM有望成为肾癌转移治疗的抗血管生成靶点。

DESCRIPTION (provided by applicant): The development and application of new molecularly based therapies is of utmost important. The key to the development of such rational therapeutic approaches lies in the identification of suitable molecular markers. Though it has been long established that tumor progression is angiogenesis dependent, fundamental questions remain regarding the characteristic differences between normal and tumor endothelial cells. Thus, novel markers, which can distinguish between normal and tumor vascular endothelium, are needed. Importantly, these markers might provide potential therapeutic targets for anti-vascular therapy. Magic roundabout (MRB) is a roundabout receptor family member with endothelial cell restricted expression. Our preliminary data shows that the MRB is highly expressed in tumor endothelium and is markedly diminished or absent in normal endothelium. Therefore in specific aim 1, we propose to take advantage of MRB's tumor endothelial restricted expression to test the hypothesis that MRB expression can be used for in vivo molecular imaging of tumor endothelium. It is expected that investing our resources in developing MRB as a tumor vascular imaging target might provide a tool to monitor the efficacy of various antiangiogenic/ vascular therapies. In specific aim 2, we propose to isolate other tumor endothelium markers (TEMs) candidates from primary renal cell cancer (RCC) and assess their expression at sites of RCC metastasis. It is hoped that some of these TEMs may serve as anti-angiogenic targets for RCC metastasis therapy.