EXPRESSION OF METALLOPROTEINASE-2 AND METALLOPROTEINASE-9 AND THEIR INHIBITORS IN RENAL-CELL CARCINOMA

Degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and MMP-9, are supposed to be key enzymes in this proc ess. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloprote inases TIMP-1 and TIMP-2 RNA using reverse transcriptase PCR technique with tumor stage in 17 samples of renal cell carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing TIMP-1 and TIMP -2 was defined to be 1 in normal kidney tissue. This MMP:TIMP ratio wa s significantly increased to 2.43 (standard deviation, SD = 0.8) in lo cally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIM P expression was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential fac tor in the aggressiveness of renal cell carcinoma.