|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥2,700,000 (Direct Cost : ¥2,700,000)
Background : Matrix metalloproteinase-2 (MMP-2) which degrades the extracellular matrix or the basement membrane has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-2, its inhibitor ; tissue inhibitor of metalloproteinases-2 (TIMP-2) and its activator ; membrane-type matrix metalloproteinase-1 (MT1-MMP) on tumor invasion or as a prognostic factor in human bladder cancer, we investigated the expression of MMP-2, TIMP-2, and MT1-MMF in bladder cancers.
Methods : Tissues obtained from 41 patients with bladder cancer were used for analysis. Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1 -MMP express ion and histologic finding or patient outcome were evaluated.
Results : Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2 <less than or equal> bladder tumors than in pTa-1 tumors (MMP-2 : p<.0005, TIMP-2 : p<
Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression were all strongly associated with decreased survival (MMP-2 : p<.0001, TIMP-2 : p<.0001, MT1-MMP : p<.005). Even within the radically cystectomized muscle invasive pT2 <less than or equal> tumor group, patients with high expression of any of these three genes had a worse prognosis than those with low expression (MMP-2 : p<.05, TIMP-2 : p<.O5, MT1-MMP : p=.