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.

（引言）我们先前报道说，肿瘤组织中肿瘤相关的巨噬细胞的密度与膀胱癌患者的预后良好相关。我们还观察到，在浸润性膀胱癌中，胸苷磷酸化酶（TP）的表达显着高于浅表膀胱癌中的表达。因此，我们分析了哪个因素对于膀胱癌的肿瘤侵袭最重要。（材料和方法）来自72例膀胱癌患者的组织标本，包括34例浸润性癌症和38种浅表癌，通过定量实时PCR（ABI PRISM 7900HT，Applied Biosystems Japan Japan Ltd）分析了表达的表达。我们分析了与肿瘤侵袭相关的各种因素的表达，例如MMP-1，MMP-2，MMP-7，MMP-9，MMP-14，MMP-14，TIMP-2，UPA，PAI-1，TS，TS，DPD，TP，TP，TP，VEGF，VEGF，vegf，vegf，72个标本。通过GAPDH表达将表达水平归一化。这些因素之间还研究了这些因素之间的相关性。（结果）实时PCR分析表明，在浅表癌中，MMP-2，MMP-9，TIMP-2，UPA，TP的表达显着更高。其中，具有最高奇数的TP似乎对于肿瘤侵袭膀胱癌最为重要。此外，TP表达与MMP-1，MMP-7，MMP-9，TIMP-2，UPA，PAI-1，DPD，VEGF的表达显着相关。然后，我们研究了2-脱氧-D-核糖的影响，这是TP酶促反应对这些因子体外表达的产物的影响。结果表明，在酸性条件下，2-脱氧-D-核糖诱导的MMP-2，MMP-9，UPA的表达。（结论）我们的结果表明，MMP-2，MMP-9，UPA和TP在膀胱癌肿瘤侵袭中起重要作用。 TP可以通过诱导其他相关因素（例如MMP-2，MMP-9，UPA，膀胱癌中的UPA）促进肿瘤侵袭。