Molecular basis of the formation of blood vessels with different structures

本研究的目的是阐明不同结构血管形成的分子基础。(1)高转移刘易斯肺癌细胞（H11）中检测到LYVE 1阳性内皮细胞（EC），而低转移细胞（P29）中未检测到LYVE 1阳性内皮细胞。(2)使用从肿瘤血管内皮细胞分离的RNA进行的DNA微阵列分析表明，LYVE 1在H11肿瘤的内皮细胞中表达上调，而NRP1表达下调。这些结果表明，H11细胞可以在其肿瘤中诱导血管样血管。(3)H11和P29细胞的表达谱分析鉴定了H11细胞中15个上调和10个下调的基因。(4)我们选择了分泌蛋白的编码基因，并构建了针对候选基因表达shRNA的慢病毒载体。然后，我们制备了表达shRNA的肿瘤细胞，将细胞移植到小鼠体内，并分析了肿瘤及其血管的形成。

The aim of this study was to clarify the molecular basis of the formation of vessels with different structures. (1) LYVE1-positive endothelial cells (ECs) were detected in tumors of high metastatic Lewis lung carcinoma cells (H11), but not in low metastatic cell (P29) tumors. (2) DNA microarray analyses using RNAs isolated from tumor vessel ECs demonstrated that LYVE1 expression was up-regulated in ECs in H11 tumor whereas NRP1 expression was down-regulated. These results suggested that H11 cells can induce lymphatic-like vessels in their tumors. (3) Expression profile analyses of H11 and P29 cells identified 15 up-regulated and 10 down-regulated genes in H11 cells. (4) We selected genes that encode secretory proteins and constructed lentiviral vectors expressing shRNAs against the candidate genes. We then prepared tumor cells expressing the shRNAs, transplanted the cells to mice, and analyzed the formation of tumors and their vessels.