Localization and quantification of mRNA for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human benign and malignant prostatic tissue

BACKGROUND. The family of matrix metalloproteinases (MMPs) has been shown t o be involved in proteolytic degradation of the extracellular matrix, which is an essential step in tumor invasion and metastasis. MMPs are tightly re gulated by the levels of active enzymes and their inhibitors, the tissue in hibitors of metalloproteinases (TIMPs). MMP-2 and its ratio to TIMP-2 have been associated with tumor recurrence and progression in a number of human malignancies. METHODS. We examined the relationship between MMP-2 and TIMP-2 mRNA express ion in 42 men with malignant (n = 32) and benign (n = 10) prostates using n onisotopic in situ hybridization and Northern blot analysis. RESULTS. mRNA for MMP-2 and TIMP-2 was localized to the malignant epithelia l cells of both high- and low-grade tumors in the periphery of the glands a nd in areas of extracapsular involvement, and to the glandular epithelium i n the benign prostates. Using Northern blot analysis, the mean MMP-2 to TIM P-2 ratio was approximately one in the benign prostates and low-grade and - stage cancers. The MMP-2 to TIMP-2 ratio increased to 3.3 in the high-grade and 2.8 in the high-stage tumors. CONCLUSIONS. The results suggest a close association between MMP-2/TIMP-2 e xpression and local tumor invasion, with a disruption in expression of the two genes leading to disease progression Future studies should focus on the activity of these enzymes and on the ratio of enzyme/inhibitor expression, which may become a useful prognostic marker in prostate cancer. Prostate 4 2:18-25, 2000. (C) 2000 Wiley-Liss, Inc.