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

Hidehiro Nomura, Noboru Fujimoto, Motoharu Seiki, Masayoshi Mai, Yasunori Okada

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

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-l) and TIMP-I 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.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalInternational Journal of Cancer
Volume69
Issue number1
DOIs
Publication statusPublished - 1996 Feb 20
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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