Expression of messenger RNAs for membrane-type 1, 2, and 3 matrix metalloproteinases in human renal cell carcinomas.

Abstract

Three different membrane-type matrix metalloproteinases (MT1, 2, and 3-MMP) that can activate proMMP-2 (progelatinase A) are thought to play an important role in invasion and metastasis by various human carcinomas. To further clarify this role, we examined mRNA expression of MT-MMPs in human renal cell carcinomas. mRNA was extracted from 25 clinical specimens of renal cell carcinoma and 23 specimens of normal renal parenchyma remote from the tumor. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was performed, and PCR products were hybridized to 32P-labeled internal probes and analyzed by a bioimage analyzer. MT1, 2, and 3-MMP mRNA expression in carcinomas was significantly higher than in normal parenchyma. In terms of the pathologic stage, MT1-MMP mRNA expression in pT2 and pT3 tumors was significantly higher than those in pT1 tumors. Although the sample size was small, it was evident that MT3-MMP mRNA expression in clear cell subtype renal cell carcinomas was higher than in the group of tumors including the granular cell subtype. These three MT-MMPs may play an important role in the pathogenesis of human renal cell carcinoma, and MT1-MMP in particular is important in invasion by carcinoma cells. It is interesting that the expression of MT3-MMP was higher in carcinomas, especially clear cell carcinoma, than in normal parenchyma, so that MT3-MMP may provide a clue an understanding of the molecular mechanism of carcinogenesis in human kidney.