Matrix metalloproteinases and their inhibitors.

Degradation of the extracellular matrix around tumour cells is an essential step in the process of tumour invasion and metastasis. The family of structurally related metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMP), play an important role in matrix degradation by tumour cells. In this paper MMP and TIMP activity was analysed in renal cell carcinoma. On the transcriptional level, RT-PCR was used to evaluate the expression of membrane type (MT) 1-MMP, MMp-2, MMP-9 and the inhibitors TIMP-1 and TIMP-2 in tumour tissue and normal kidney tissue. Zymography and reverse zymorgaphy measured the activity of MMPs and TIMPs in the supernatant of primary cell cultures derived from these tumour tissues at the protein level. In addition, MMP and TIMP serum levels of these patients were analysed before and 7 days after tumour nephrectomy. MMP expression revealed to be five times higher in low graded tumour tissue compared to normal kidney tissue. In the supernatant of the cell cultures, both MMP-2 and TIMP protein level was higher in samples derived from advanced carcinoma compared to samples derived from organ confined tumours. Serum levels of TIMP-2 decreased significantly after tumour nephrectomy. In conclusion, MMPs are key enzymes for tumour progression in renal cell carcinoma. New functions especially concerning the TIMP proteins may provide further understanding of the tumour progression processes.