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至关重要。开发这种合理的治疗方法的关键在于鉴定合适的分子标记物。虽然肿瘤的进展是血管生成依赖性的，但关于正常和肿瘤内皮细胞之间的特征差异的基本问题仍然存在。因此，需要能够区分正常和肿瘤血管内皮的新标记物。重要的是，这些标志物可能为抗血管治疗提供潜在的治疗靶点。 Magic roundabout（MRB）是一种在内皮细胞中表达的环状受体家族成员。我们的初步数据显示，MRB在肿瘤内皮细胞中高度表达，而在正常内皮细胞中显著减少或缺失。因此，在具体目标1中，我们提出利用MRB的肿瘤内皮限制性表达来测试MRB表达可用于肿瘤内皮的体内分子成像的假设。预计将我们的资源投资于开发MRB作为肿瘤血管成像靶点可能会提供一种工具来监测各种抗血管生成/血管治疗的疗效。在具体目标2中，我们提出从原发性肾细胞癌（RCC）中分离其他肿瘤内皮标志物（TEM）候选物，并评估它们在RCC转移部位的表达。希望这些TEM中的一些可以作为RCC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.