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Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas
Author(s) -
Nomura Hidehiro,
Fujimoto Noboru,
Seiki Motoharu,
Mai Masayoshi,
Okada Yasunori
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960220)69:1<9::aid-ijc3>3.0.co;2-8
Subject(s) - matrix metalloproteinase , gelatinase , gelatinase a , metalloproteinase , matrix (chemical analysis) , matrix metalloproteinase 9 , cancer research , chemistry , medicine , chromatography
We examined the production and tissue localization of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gastric carcinoma tissues. MMP‐I (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‐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‐I 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. © 1996 Wiley‐Liss, Inc.