Linked Life Data

15185339

Source:http://linkedlifedata.com/resource/pubmed/id/15185339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-8
pubmed:abstractText
The effects of glycine-extended gastrin (G-Gly) on the invasion by colon cancer cells through stromal extracellular matrix and the role of metalloproteinases (MMPs) in this invasion were investigated. We found that 10(-9)-10(-6) M G-Gly significantly increased the invasiveness of 2 human colon cancer cell lines, LoVo and HT-29, both expressing the G-Gly-specific binding site but little gastrin/CCK-B receptor (gastrin receptor). LoVo cells expressed MMP-1, -2, -3 and -9. An amount of 10(-7) M G-Gly enhanced collagenase MMP-1 expression. Overexpression of enhanced green fluorescent protein (EGFP)-fused MMP-1 in LoVo cells, by cDNA transfection, enhanced invasiveness through type I collagen gel. Immunofluorescence study revealed that G-Gly increased the number of cytoplasmic vesicles containing MMP-1, some vesicles being released from the cells. The MMP-1 vesicles contained one of the ubiquitous coat proteins, Golgi-localized, gamma-adaptin ear-containing, ARF-binding proteins-2 (GGA-2). MMP-1 also colocalized with CD147 (EMMPRIN, an extracellular matrix metalloproteinase inducer in adjacent stromal cells). It was suggested that G-Gly increased the number of vesicles containing MMP-1 and that MMP-1 interacted with CD147 to increase invasion. G-Gly significantly enhanced the production of MMP-3, an activator of MMP-1 and -9, as well as gelatinase MMP-9 activity. The G-Gly-mediated MMP-9 increase was inhibited by treatment with anti-MMP-3 IgG and MMP-3 siRNA. Furthermore, G-Gly increased the proMMP-2 level, although no activated MMP-2 was found in conditioned medium in either the presence or the absence of G-Gly. By contrast, gastrin (10(-7) M) had no effect on the levels of these MMPs or the invasiveness of colon cancer cells in type I collagen gel and Matrigel. These effects of G-Gly on the activity and expression of MMPs and the invasiveness of colon cancer cells were inhibited by treating the cells with a broad-spectrum metalloproteinase inhibitor (CGS27023A) and nonselective gastrin/CCK receptor antagonists (proglumide and benzotript). But a gastrin/CCK-B receptor antagonist (YM022) did not inhibit the increased invasion by G-Gly. Together, these results demonstrate that G-Gly renders colon cancer cells more invasive by increasing MMP-1 and MMP-3 expressions via the putative G-Gly receptor and would thus be a good molecular target in a clinical setting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Biocompatible Materials, http://linkedlifedata.com/resource/pubmed/chemical/Collagen, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations, http://linkedlifedata.com/resource/pubmed/chemical/Gastrins, http://linkedlifedata.com/resource/pubmed/chemical/Gels, http://linkedlifedata.com/resource/pubmed/chemical/Laminin, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/matrigel, http://linkedlifedata.com/resource/pubmed/chemical/tyrosyl-glycyl-tryptophyl-methionyl-...
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-31
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel.
pubmed:affiliation
Department of Pathology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. baba-mi@mc.pref.osaka.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't