Matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in sera and urine of patients with renal carcinoma

The matrix metalloproteinase (MMP) family has been shown to play a critical role in tissue remodeling and tumor infiltration. Their activity is normally strictly controlled by tissue inhibitors of metalloproteinases (TIMPs). However, TIMPs act indirectly through modulation of protease activity or directly through cell surface receptors to direct cell fate. These molecules have been proposed as markers of malignant cancer. Previous studies on MMP and TIMP expression in kidney carcinoma have been limited and have reported variable observations. The current study measured the content of MMP-2 and -9 and TIMP-1 and -2 in the sera and urine of patients with kidney carcinoma by enzyme-linked immunosorbent assay. Of these patients, 16 exhibited clear cell renal cell carcinoma (ccRCC) and 4 exhibited oncocytoma. Sera and urine samples of 53 healthy subjects were used as controls. In the sera of the control group, MMP-2 and TIMP-2 were detectable in all samples, while MMP-9 and TIMP-1 were below the sensitivity of the assay. In the pathological specimens, the mean serum values of MMP-2 and TIMP-1 and -2 were similar in the ccRCC and oncocytoma patients, whereas the value for MMP-9 was 2-fold higher in the ccRCC patients compared with the oncocytoma patients. With regard to the urine specimens, all four molecules were undetectable in the normal healthy samples and in a few pathological samples. The mean values for MMP-2 and -9 and TIMP-2 in the positive urine specimens were similar in the ccRCC and oncocytoma patients, whereas the mean value of TIMP-1 was higher in the ccRCC patients compared with that of the oncocytoma patients. The mean urinary levels of the four molecules were less than those of the sera. Statistical analysis of the data did not reveal any correlation between the tumor grades and expression levels of the molecules examined.