Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

• Published in: International Brazilian journal of urology Vol. 38; no. 2; pp. 167 - 174
• Main Authors: Reis, Sabrina Thalita, Antunes, Alberto Azoubel, Pontes-Junior, Jose, Sousa-Canavez, Juliana Moreira de, Dall'Oglio, Marcos Francisco, Piantino, Camila Belfort, Cruz, Jose Arnaldo Shiomi da, Morais, Denis Reis, Srougi, Miguel, Leite, Katia Ramos Moreira
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Urologia 01.04.2012
• Subjects: Adult; Aged; diagnosis; Gene Expression; Humans; Interleukin-8 - metabolism; Male; matrix metalloproteinase; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase 2 - metabolism; Middle Aged; Neoplasm Grading; neoplasms; prognosis; prostate; Prostate-Specific Antigen - blood; Prostatectomy; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Tissue Inhibitor of Metalloproteinase-2 - metabolism
• ISSN: 1677-5538; 1677-6119; 1677-5538
• DOI: 10.1590/S1677-55382012000200004

Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.