Expression of metalloproteinase 2 and 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 process. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloproteinases 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 was significantly increased to 2.43 (standard deviation, SD = 0.8) in locally 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:TIMP 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 factor in the aggressiveness of renal cell carcinoma.
Kugler
A
A
Department of Urology and Pathology, Georg-August-University, Göttingen, Germany.
Hemmerlein
B
B
Thelen
P
P
Kallerhoff
M
M
Radzun
H J
HJ
Ringert
R H
RH
D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis*; D018093:Gelatinases / Q000096:biosynthesis*; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*
D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9