Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-9-24
pubmed:abstractText
Gastric carcinomas can be classified into scirrhous carcinomas (SC), i.e. 'linitis plastica' or Borrmann 4 gastric cancer, and non-scirrhous carcinomas (NSC). SC are characterized by diffuse invasive growth patterns with marked fibrosis, frequent peritoneal dissemination and lymph-node metastases and poor prognosis, while NSC show medullary growth patterns and common hematogenous metastases. To study the differences in local expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between SC and NSC, we examined the expression of MMPs and TIMPs in human gastric carcinoma tissues by several methods including sandwich-enzyme immunoassay systems, gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR, immunoblotting, immunohistochemistry and in situ zymography. Of the seven MMPs and two TIMPs tested, only proMMP-2 levels were remarkably higher in SC than in NSC (P < 0.01), and proMMP-2 activation ratio was significantly lower in SC than in NSC (P < 0.05). TIMP-3 mRNA levels were remarkably about 2-fold higher in SC than in NSC tissues (P < 0.01). TIMP-3 production in SC was confirmed by immunoblotting and TIMP-3 was immunolocalized to stromal fibroblasts in SC. TIMP-3 mRNA levels inversely correlated with proMMP-2 activation ratios, although the expression levels of MT1-MMP and MT2-MMP were not different in SC and NSC. By in situ zymography, gelatinolytic activity appeared to be weaker in SC than in NSC. All these data suggest that proMMP-2 activation is down-regulated by TIMP-3 expressed in scirrhous gastric carcinomas. Our findings may explain the differences in clinical behaviors of SC and NSC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0262-0898
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
223-33
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15387372-Adenocarcinoma, Scirrhous, pubmed-meshheading:15387372-Aged, pubmed-meshheading:15387372-Aged, 80 and over, pubmed-meshheading:15387372-Base Sequence, pubmed-meshheading:15387372-Blotting, Western, pubmed-meshheading:15387372-DNA Primers, pubmed-meshheading:15387372-Enzyme Activation, pubmed-meshheading:15387372-Enzyme Precursors, pubmed-meshheading:15387372-Female, pubmed-meshheading:15387372-Gelatin, pubmed-meshheading:15387372-Gelatinases, pubmed-meshheading:15387372-Humans, pubmed-meshheading:15387372-Immunoenzyme Techniques, pubmed-meshheading:15387372-Immunohistochemistry, pubmed-meshheading:15387372-Male, pubmed-meshheading:15387372-Metalloendopeptidases, pubmed-meshheading:15387372-Middle Aged, pubmed-meshheading:15387372-RNA, Messenger, pubmed-meshheading:15387372-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15387372-Stomach Neoplasms, pubmed-meshheading:15387372-Tissue Inhibitor of Metalloproteinase-3
pubmed:year
2004
pubmed:articleTitle
Differences between scirrhous and non-scirrhous human gastric carcinomas from the aspect of proMMP-2 activation regulated by TIMP-3.
pubmed:affiliation
Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't