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

Autor(es)

Reis, Sabrina Thalita ^{[1, 2]} ; Antunes, Alberto Azoubel ^{[1, 2]} ; Pontes-Junior, Jose ^{[1, 2]} ; de Sousa-Canavez, Juliana Moreira ; Dall'Oglio, Marcos Francisco ^{[1, 2]} ; Piantino, Camila Belfort ^[1] ; Shiomi da Cruz, Jose Arnaldo ^{[1, 3]} ; Morais, Denis Reis ^[1] ; Srougi, Miguel ^{[1, 2]} ; Leite, Katia R. M. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Urol, Lab Med Invest LIM55, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, ICESP, Dept Urol, Urooncol Grp, Sao Paulo - Brazil

^[3] Genoa Biotechnol SA, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL BRAZ J UROL; v. 38, n. 2, p. 167-174, MAR-APR 2012.
• Citações Web of Science: 17

Resumo

OBJECTIVE: 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 specific 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). MATERIALS AND METHODS: 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 final outcome of the PCa. RESULTS: 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). CONCLUSION: 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. (AU)

• Processo FAPESP: 09/50368-9 - Análise da expressão das metaloproteinases da matriz -2 e -9, e de seus reguladores MT1-MMP, TIMP-1, TIMP-2, RECK, TGF-beta e interleucina-8 por PCR quantitativo em tempo real em câncer de próstata e bexiga
• Beneficiário: Kátia Ramos Moreira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Regular