Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas

Int J Cancer. 1996 Feb 20;69(1):9-16. doi: 10.1002/(SICI)1097-0215(19960220)69:1<9::AID-IJC3>3.0.CO;2-8.


We examined the production and tissue localization of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gastric carcinoma tissues. MMP-1 (tissue collagenase), MMP-9 (gelatinase B) and TIMP-2 were immunolocalized in carcinoma cells and MMP-2 (gelatinase A) on tumor cell membranes, whereas no or little immunostaining for MMP-3 (stromelysin-1) and TIMP-1 was seen in carcinoma cells. Stromal cells in carcinoma tissue were also positively stained for these MMPs and TIMPs. MMP-2 immunostaining was observed exclusively on advanced gastric carcinoma cells and correlated with vascular invasion by tumor cells. Sandwich enzyme immunoassays revealed enhanced production of MMP-1, MMP-2, MMP-3, MMP-9 and TIMP-1 by carcinoma tissues. Gelatinolytic activities were significantly higher in carcinoma samples than in normal controls. Using gelatin zymography, active forms of MMP-2 and MMP-9 were more frequently detected in carcinoma tissue, and the activation rate of the zymogen of MMP-2 (proMMP-2), but not that of proMMP-9, correlated well with degree of local invasion and lymphatic permeation. Our data indicate an enhanced production of 4 MMPs in gastric carcinoma tissue and suggest that activation of pro-MMP-2 may be a key step for spreading of gastric carcinoma cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • Gelatinases / metabolism*
  • Glycoproteins / biosynthesis
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / metabolism*
  • Protein Biosynthesis
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Tissue Inhibitor of Metalloproteinase-2
  • Tissue Inhibitor of Metalloproteinases


  • Enzyme Precursors
  • Glycoproteins
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2