Analysis of the Molecular mechanism of the function of Thymidine phosphorylase on tumor immunology, angiogenesis, invasion and metastasis.

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Thymidine phosphorylase(TP) is a enzyme that is reported to increase the expression in various kinds of tumors. TP involved in tumor proliferation, invasion, and metastasis and tumor angiogenesis. TP is also highly expressed in Macrophages. And it is supposed to involve in tumor immunology. We tried to analyze the roles of TP on the tumor immunology, inflammation, tumor invasion. We found1 TP protein has leucine zipper motif.2 Estimate the IL-10 promoter activity when TP is transiently coexpressed with Il-10 promoter. TP protein did not induce the IL-10 transcription. Significantly.3 Quantify the mRNA expression level of MMP1,2,7,9,14 and uPA, VEGF and TP in 72 bladder cancers by real-time PCR analysis. The expression levels of TP in invasive tumors were significantly higher than in superficial bladder tumors. Furthermore the expression level of TP significantly correlated with that of MMP-9, uPA, TIMP-2, MMP-1, MMP-7 and VEGF.We generated the TP overexpressed EJ-1 and BT bladder carcinoma cells, EJ/TP and BT/TP respectively. But the m RNA levels of MMP-9 in EJ/TP and BT/TP cells is comparable of that in EJ/CV and BT/CV cells.4 2-deoxy-D-ribose(2DR), produced by the catalytic action of TP on thymidine, enhanced the expression level of MMP-9, uPA, and MMP-1 efficiently in THP-1 cells.5.2-deoxy-L-ribose(2LR) that is stereoisomer of 2DR suppressed the tumor invasion and metastaisi KB/TP tumors that were xenografted in nude mice.