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 to be involved in proteolytic degradation of the extracellular matrix, which is an essential step in tumor invasion and metastasis. MMPs are tightly regulated by the levels of active enzymes and their inhibitors, the tissue inhibitors 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 expression in 42 men with malignant (n = 32) and benign (n = 10) prostates using nonisotopic in situ hybridization and Northern blot analysis.


RESULTS
mRNA for MMP-2 and TIMP-2 was localized to the malignant epithelial cells of both high- and low-grade tumors in the periphery of the glands and in areas of extracapsular involvement, and to the glandular epithelium in the benign prostates. Using Northern blot analysis, the mean MMP-2 to TIMP-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 expression 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.
Still
K
K
Department of Surgery, School of Surgical Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom.
Robson
C N
CN
Autzen
P
P
Robinson
M C
MC
Hamdy
F C
FC
D015152:Blotting, Northern; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D011467:Prostate / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2