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Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human urothelial
1Department of Urology, Kanazawa University School of Medicine, Japan.
Purpose:
Three different membrane-type matrix metalloproteinases (MT1, 2, 3-MMP) which can activate proMMP-2 (progelatinase A) are thought to have an important role in various human carcinoma invasions and metastases. We examined the mRNA expression of MT-MMPs and the tissue immunolocalization of MT1-MMP in human urothelial carcinomas.
Materials And Methods:
mRNA was extracted from 27 clinical urothelial carcinomas and 10 normal urothelial mucosa tissues remote from the tumor. RT-PCR using specific primers was performed, and PCR products were hybridized to 32P-labeled internal probes and analyzed by a bioimage analyzer. Immunolocalization was studied using a monoclonal antibody against MT1-MMP (114-6G6).
Results:
MT1-MMP and MT2-MMP mRNA expressions in urothelial carcinomas were significantly higher than those in the normal mucosa. In contrast, MT3-MMP mRNA was little expressed in both tissues, and the amount of MT3-MMP mRNA appeared to be much lower than MT1-MMP and MT2-MMP in the tissue samples. In terms of the tumor multiplicity, MT1-MMP and MT2-MMP mRNA expressions in the group of multiple tumors were significantly higher than those in the solitary tumor group. The carcinoma cells were immunostained for MT1-MMP predominantly in invasive and superficial carcinoma cells. The immunoreactivity was more intense in the invasive type than in the superficial type.
Conclusions:
It is suggested that MT1-MMP and MT2-MMP play an important role in the development of human urothelial carcinomas and reflect some aspects of the pathogenesis of multifocal occurrence. In spite of the possible contribution to the invasive and metastatic phenotype, MT1-MMP mRNA and its product are thought to be expressed already in the clinical superficial stage in some cases of this tumor type.
Insights
Membrane-type matrix metalloproteinases (MT1-MMP and MT2-MMP) are upregulated in urothelial carcinomas, suggesting their role in tumor development and multifocal occurrence. MT1-MMP is also found in superficial and invasive cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are crucial in tissue remodeling.
- Membrane-type MMPs (MT-MMPs) activate proMMP-2, a key enzyme in cancer invasion.
- MT1, MT2, and MT3-MMP are implicated in human carcinoma progression.
Purpose of the Study:
- To investigate the mRNA expression of MT1, MT2, and MT3-MMP in human urothelial carcinomas.
- To determine the tissue immunolocalization of MT1-MMP in these tumors.
Main Methods:
- RNA extraction from 27 urothelial carcinomas and 10 normal tissues.
- RT-PCR with specific primers to analyze MT-MMP mRNA expression.
- Immunohistochemistry using a monoclonal antibody to detect MT1-MMP protein.
Main Results:
- MT1-MMP and MT2-MMP mRNA levels were significantly higher in carcinomas than normal mucosa.
- MT3-MMP mRNA expression was low in both tumor and normal tissues.
- Higher MT1-MMP and MT2-MMP mRNA expression correlated with multiple tumors compared to solitary tumors.
- MT1-MMP protein was detected in both superficial and invasive urothelial carcinoma cells, with stronger staining in invasive types.
Conclusions:
- MT1-MMP and MT2-MMP are likely involved in the pathogenesis and multifocal development of urothelial carcinomas.
- MT1-MMP expression, at both mRNA and protein levels, is present even in early-stage superficial carcinomas, suggesting a role in initial tumor progression.