[mRNA expression analysis of metastatic markers in clear-cell renal cell carcinoma]

Deregulated expression of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs) is an important pre-requisite for metastatic processes in a variety of human tumor types including renal cell cancer. Own previous cDNA microarray studies demonstrated differential expression of several MMPs and TIMPs in normal renal tissue and renal cancer cell lines. In order to analyze MMP/TIMP expression in primary clear-cell renal cell carcinoma (ccRCC) tissues we have determined the mRNA abundance of MMP-2, MMP-9, TIMP-1 and TIMP-2 by RT-PCR in 29 ccRCC and 7 normal renal tissues. Compared to normal renal tissue, expression of MMP-2 and TIMP-2 was significantly reduced in 16 and 12 of 29 ccRCCs, respectively. In contrast, MMP-9 expression was significantly increased in 11 of 29 ccRCCs. No difference was seen for TIMP-1 transcription levels. Because expression of the metastasis-associated CXCR4 chemokine receptor is increased and associated with poor tumour-specific survival in ccRCC we also compared MMP/TIMP and CXCR4 expression in the given tissue samples. Expression of TIMP-1 and TIMP-2 did not correlate with CXCR4 expression levels, whereas mRNA expression of MMP-2 and MMP-9 was significantly higher in tumours with strong CXCR4 expression (p = 0.04 and p = 0.01, respectively). These preliminary results suggest the involvement of CXCR4, MMP-2, and MMP-9 in renal cancer progression.