Functional analysis of the lymphatic system in normal and diseased tissue

尽管淋巴管系统在恶性肿瘤的转移扩散中起着重要作用，但由于缺乏特异的淋巴标志物和生长因子，对淋巴系统的研究一直受到阻碍。新近发现的透明质酸(HA)受体LYVE-1主要局限于淋巴管内皮细胞。由于HA是肿瘤细胞迁移的关键介质，我们希望分析LYVE-1在肿瘤进展和转移中的作用。为此，我们将使用过表达可溶性Lyve-1蛋白的MDA-MB-435乳腺癌细胞进行小鼠异种移植研究。除了了解淋巴管的结构成分外，我们还致力于建立一种在Lyve-1启动子控制下过表达hrGFP的小鼠遗传模型。除了特定淋巴管启动子的特征外，这个小鼠模型还将使我们能够创建组织特异性转基因和(Cre-lox)基因敲除小鼠。毫无疑问，这些工具将在癌症转移领域带来更多令人兴奋和相关的研究。

Although the lymphatic vasculature plays important roles in the metastatic spread of malignant tumors, studies of the lymphatic system have been hindered by the lack of specific lymphatic markers and growth factors. The recently identified hyaluronan (HA) receptor LYVE-1 is largely restricted to lymphatic endothelial cells. Since HA is a key mediator of tumor cell migration, we wish to analyze the role of LYVE-1 in tumor progression and metastasis. To this end we will perform mouse xenotransplantation studies using MDA-MB-435 breast cancer cells transfected to overexpress soluble LYVE-1 proteins. Beside the knowledge of the structural components of the lymphatic vessels, we are also pursuing to establishing a genetic mouse model overexpressing hrGFP under the control of the LYVE-1 promoter. In addition to the characterization of a specific lymphatic vessel promoter, this mouse model will enable us to create tissue specific transgenic as well as (Cre-lox) knockout mice. These tools will without any doubt lead to further exciting and relevant research in the field of cancer metastasis.