Relationship between metalloprotease expression in tumour and stromal cells and aggressive behaviour in prostate carcinoma: Simultaneous high-throughput study of multiple metalloproteases and their inhibitors using tissue array analysis of radical prostatectomy samples

Scand J Urol Nephrol. 2011 Apr;45(3):171-6. doi: 10.3109/00365599.2010.545074. Epub 2011 Jan 18.

Abstract

Objective: The aim of this study was to detect a potential association between clinicopathological factors of prostate cancer aggressiveness and the expression of matrix metalloproteases and their inhibitors in tumour and stromal cells.

Material and methods: A tissue array technique and immunochemistry with specific antibodies against matrix metalloproteinases (MMPs)-1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors (TIMPs)-1, 2 and 3 were used to analyse the surgical specimens of 133 patients treated by radical prostatectomy. For each antibody preparation, the cellular location of immunoreactivity was determined.

Results: The expression of MMP-2 was negatively associated with high tumour grade. With regard to stromal fibroblasts, TIMP-3 expression was positively associated with histological grade. MMP-7 expression was negatively associated with pretreatment serum levels of PSA, whereas MMP-13 was positively associated with higher levels of the antigen. TIMP-2 expression by mononuclear inflammatory cells correlated significantly and negatively with tumour grade.

Conclusions: The expression of TIMP-3 by fibroblasts was associated with a higher Gleason score. An increased expression of MMP-13 by fibroblasts was associated with a greater preoperative level of PSA. In contrast, MMP-2 expression by tumour as well as TIMP-2 expression by peritumoral inflammatory cells was associated with less aggressive prostate carcinoma characteristics.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / epidemiology
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • High-Throughput Screening Assays
  • Humans
  • Male
  • Metalloproteases / metabolism*
  • Middle Aged
  • Prostatectomy*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Stromal Cells / metabolism
  • Tissue Array Analysis*
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Tissue Inhibitor of Metalloproteinases
  • Metalloproteases