title: Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer.
abstract: 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 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).
  
  
  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 fi nal 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Medical Investigation-LIM55, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Sabrina Thalita
authors.initials: ST
authors.lastname: Reis
authors.forename: Alberto Azoubel
authors.initials: AA
authors.lastname: Antunes
authors.forename: Jose
authors.initials: J
authors.lastname: Pontes-Junior
authors.forename: Juliana Moreira de
authors.initials: JM
authors.lastname: Sousa-Canavez
authors.forename: Marcos Francisco
authors.initials: MF
authors.lastname: Dall'Oglio
authors.forename: Camila Belfort
authors.initials: CB
authors.lastname: Piantino
authors.forename: Jose Arnaldo Shiomi da
authors.initials: JA
authors.lastname: Cruz
authors.forename: Denis Reis
authors.initials: DR
authors.lastname: Morais
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.forename: Katia Ramos Moreira
authors.initials: KR
authors.lastname: Leite
mesh_terms: D000328:Adult; D000368:Aged; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D017430:Prostate-Specific Antigen; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14