Molecular basis of the formation of blood vessels with different structures

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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.