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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
Author(s) -
Still Karen,
Robson Craig N.,
Autzen Pernille,
Robinson Mary C.,
Hamdy Freddie C.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(20000101)42:1<18::aid-pros3>3.0.co;2-a
Subject(s) - matrix metalloproteinase , tissue inhibitor of metalloproteinase , pathology , metastasis , extracellular matrix , in situ hybridization , tumor progression , northern blot , cancer , immunohistochemistry , matrix metalloproteinase inhibitor , biology , prostate , matrilysin , cancer research , western blot , prostate cancer , medicine , gene expression , gene , microbiology and biotechnology , biochemistry
Abstract 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. Prostate 42:18–25, 2000. © 2000 Wiley‐Liss, Inc.