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

胸苷磷酸化酶对肿瘤免疫、血管生成、侵袭和转移作用的分子机制分析。

基本信息

批准号：
15590278
负责人：
HARAGUCHI Misako
金额：
$ 2.37万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590278/
关键词：
Thymidine phosphorylase MMP invasion 2-deoxy-D-ribose IL-10

项目摘要

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.

胸苷磷酸化酶（TP）是一种在多种肿瘤中表达增加的酶。TP参与肿瘤的增殖、侵袭、转移和肿瘤血管生成。TP在巨噬细胞中也高度表达。它可能与肿瘤免疫学有关。本文试图分析TP在肿瘤免疫、炎症、肿瘤侵袭等方面的作用。我们发现1 TP蛋白具有亮氨酸拉链结构。2检测TP与IL-10启动子瞬时共表达时IL-10启动子的活性。TP蛋白不诱导IL-10的转录。3应用实时荧光定量PCR技术检测72例膀胱癌组织中MMP 1、2、7、9、14和uPA、VEGF、TP的mRNA表达水平。TP在浸润性膀胱肿瘤中的表达水平明显高于浅表性膀胱肿瘤。TP与MMP-9、uPA、TIMP-2、MMP-1、MMP-7和VEGF的表达水平呈显著正相关。但MMP-9在EJ/TP和BT/TP细胞中的mRNA水平与EJ/CV和BT/CV细胞相当。4 2-脱氧-D-核糖（2DR），由TP对胸苷的催化作用产生，增强MMP-9，uPA，5.2-脱氧-L-核糖（2LR）是2DR的立体异构体，它抑制肿瘤的侵袭和转移。在裸鼠中异种移植的TP肿瘤。