Evidence for Increased Activated Metalloproteinase 2 (MMP-2a) Expression Associated With Human Prostate Cancer Progression

Oncol Res. 1996;8(2):69-75.

Abstract

Immunolabeling studies have previously indicated that increased expression of the 72-kDa matrix metalloproteinase 2 (MMP-2) is associated with human prostate cancer progression. It is not known if the enzymatically active MMP-2 is expressed in prostate cancer and if increased expression is associated with progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP-2a, 66 kDa) were used (along with previously developed MMP-2 antibodies) to investigate the expression of MMP-2a and MMP-2 in human prostate tissue extracts. SDS-PAGE, Western blots, and zymography indicated that MMP-2a expression was undetectable in normal prostate (n = 6), benign prostatic hyperplasia (n = 9), and in prostate cancer of low Gleason score (GS) 4 (n = 11). MMP-2a was expressed in prostate cancer of increased GS (n = 37) and in lymph node metastases (n = 7). Quantitative ELISAs of human prostate cancer tissue extracts revealed that the levels of MMP-2 and MMP-2a per microgram of protein increased in prostate cancer tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph node metastases, but MMP-2 was not expressed or was barely detectable in these tissues. The molar ratios of MMP-2a to MMP-2 increased from 0 to 6.23 in tissues of GS 4 to 10, respectively. We conclude that significant increases in MMP-2a are associated with the malignant progression of prostate cancer and with tumor cell metastases to lymph nodes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Disease Progression
  • Enzyme Activation
  • Enzyme-Linked Immunosorbent Assay
  • Gelatinases / metabolism*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / metabolism*
  • Neoplasm Proteins / metabolism*
  • Prostate / enzymology*
  • Prostatic Hyperplasia / enzymology*
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / pathology

Substances

  • Neoplasm Proteins
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2