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Role of tumor-associated macrophage in tumor invasion and inhibition of tumor invasion in urothelial cancers

肿瘤相关巨噬细胞在尿路上皮癌肿瘤侵袭和抑制肿瘤侵袭中的作用

基本信息

批准号：
12671546
负责人：
NAKAGAWA Masayuki
金额：
$ 2.24万
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：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

(Introduction) we previously reported that the density of tumor-associated macrophage (TAM) in tumor tissue was well correlated with prognosis of bladder cancer patients. We also observed that the expression of thymidine phosphorylase (TP), one of the potent angiogenic factors, is significantly higher in invasive bladder cancers than that in superficial bladder cancers. Therefore we analyzed which factor was most important for the tumor invasion of bladder cancers. (Materials and Methods) Tissue specimens from 72 patients with bladder cancer, including 34 invasive cancers and 38 superficial cancers were analyzed for the expression by quantitative real-time PCR(ABI PRISM 7900HT, Applied Biosystems Japan Ltd). We analyzed the expression of various factors related with tumor invasion, such as MMP-1, MMP-2, MMP-7, MMP-9, MMP-14, TIMP-2, uPA, PAI-1, TS, DPD, TP, VEGF in 72 specimens. The expression level was normalized by GAPDH expression. Correlation among these factors was also investigated in the study. (Results) Real-time PCR analysis revealed that the expression of MMP-2, MMP-9, TIMP-2, uPA, TP was significantly higher in invasive cancers that in superficial cancers. Among them, TP with the highest odd-ratio seems to be most important for tumor invasion of bladder cancer. Furthermore, TP expression was significantly correlated with expression of MMP-1, MMP-7, MMP-9, TIMP-2, uPA, PAI-1, DPD, VEGF. We then investigated the effect of 2-deoxy-D-ribose, a product of TP enzymatic reaction on expression of these factors in vitro. The results showed that 2-deoxy-D-ribose induced expression of MMP-2, MMP-9, uPA in the acidic condition. (Conclusion) Our results suggest that MMP-2, MMP-9, uPA and TP plays important roles in tumor invasion of bladder cancer. TP may promote tumor invasion by induction of other invasion related factors, such as MMP-2, MMP-9, uPA in bladder cancers.

(导言)我们曾报道肿瘤组织中肿瘤相关巨噬细胞()的密度与膀胱癌患者的预后密切相关。我们还观察到浸润性膀胱癌中潜在的血管生成因子胸苷磷酸化酶(TP)的表达显著高于浅表性膀胱癌。因此，我们分析了哪种因素对膀胱癌的侵袭最重要。(材料与方法)应用实时荧光定量聚合酶链式反应技术(ABI PRISM 7900HT)对72例膀胱癌组织标本进行检测，其中浸润性膀胱癌34例，浅表性膀胱癌38例。分析72例乳腺癌组织中与肿瘤侵袭相关的各种因子的表达情况，包括：基质金属蛋白酶-1、基质金属蛋白酶-2、基质金属蛋白酶-7、基质金属蛋白酶-9、基质金属蛋白酶-14、基质金属蛋白酶-2、尿激酶型纤溶酶原激活剂、纤溶酶原激活物-1、TS、DPD、TP、血管内皮生长因子。用GAPDH表达对表达水平进行归一化。研究中还对这些因素之间的相关性进行了研究。(结果)实时定量聚合酶链式反应分析显示，浸润性癌组织中MMP2、MMP9、TIMP-2、uPA、TP的表达明显高于浅表性癌。其中，TP的奇数比最高，似乎对膀胱癌的侵袭最为重要。TP的表达与MMP1、MMP7、MMP9、TIMP 2、uPA、PAI 1、DPD、VEGF的表达呈正相关。然后，我们在体外研究了茶多酚的酶促反应产物2-脱氧-D-核糖对这些因子表达的影响。结果表明，2-脱氧-D-核糖在酸性条件下可诱导MMP2、MMP9、uPA的表达。(结论)MMP2、MMP9、uPA和TP在膀胱癌的侵袭过程中起重要作用。TP可能通过诱导其他侵袭相关因子如MMP2、MMP9、uPA等促进膀胱癌的侵袭。