Source:http://linkedlifedata.com/resource/pubmed/id/12845672
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2003-7-7
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pubmed:abstractText |
Our study examined the in vitro and in vivo responses of a newly discovered HGF/SF antagonist, NK4, on HGF/SF-promoted growth of human prostate cancer cells (PC-3). Nude mice were s.c. injected with either PC-3- and/or HGF/SF-producing fibroblasts (MRC5), and tumor size was measured over a 4-week period. rh-HGF/SF and/or NK4 were introduced by osmotic minipumps. An in vitro study found that NK4 significantly suppressed HGF/SF-induced invasion (HGF/SF; p < 0.01 vs. HGF/SF+NK4) and migration (HGF/SF; p < 0.05 vs. HGF/SF+NK4). Similarly, NK4 also suppressed the invasion (MRC5; p < 0.01 vs. MRC5+NK4) and migration (MRC5; p < 0.05 vs. MRC5+NK4) induced by MRC5 cells. NK4 also suppressed HGF/SF- and MRC5-induced tyrosine phosphorylation of the HGF/SF receptor Met as assessed by immunoprecipitation. Using a nude mouse model, prostate tumor volume (mm(3)) was significantly increased in both HGF/SF- (HGF/SF; p < 0.05 vs. control) and MRC5- (MRC5; p < 0.01 vs. control) treated groups compared to the control. In contrast, NK4 alone significantly reduced the growth of prostate tumors (NK4; p < 0.01 vs. control). In addition, NK4 also suppressed both HGF/SF- (HGF/SF; p < 0.01 vs. HGF/SF+NK4) and MRC5- (MRC5; p < 0.05 vs. MRC5+NK4) induced tumor growth in vivo by significantly reducing (p < 0.05) the degree of tumor angiogenesis using a recently discovered family of tumor endothelial markers (TEMs) by Q-RT-PCR analysis. In conclusion, NK4 suppresses both HGF/SF- and MRC5-induced invasion/migration of PC-3 cells in vitro. Furthermore, the HGF/SF antagonist NK4 significantly reduces prostate tumor growth in vivo by inhibiting the degree of tumor angiogenesis as determined by TEM-1 and TEM-8. Finally, our study provides evidence of the therapeutic potential of NK4 in prostate cancer development by antagonising HGF/SF-mediated events.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HGF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Lactamases,
http://linkedlifedata.com/resource/pubmed/chemical/beta-lactamase TEM-1,
http://linkedlifedata.com/resource/pubmed/chemical/beta-lactamase TEM-2
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
348-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12845672-Animals,
pubmed-meshheading:12845672-Blotting, Western,
pubmed-meshheading:12845672-Cell Adhesion,
pubmed-meshheading:12845672-Cell Division,
pubmed-meshheading:12845672-Cell Movement,
pubmed-meshheading:12845672-Female,
pubmed-meshheading:12845672-Fibroblasts,
pubmed-meshheading:12845672-Hepatocyte Growth Factor,
pubmed-meshheading:12845672-Humans,
pubmed-meshheading:12845672-Male,
pubmed-meshheading:12845672-Mice,
pubmed-meshheading:12845672-Mice, Nude,
pubmed-meshheading:12845672-Mitogens,
pubmed-meshheading:12845672-Neoplasm Invasiveness,
pubmed-meshheading:12845672-Neovascularization, Pathologic,
pubmed-meshheading:12845672-Phosphoproteins,
pubmed-meshheading:12845672-Phosphorylation,
pubmed-meshheading:12845672-Prostatic Neoplasms,
pubmed-meshheading:12845672-Proto-Oncogene Proteins c-met,
pubmed-meshheading:12845672-Survival Rate,
pubmed-meshheading:12845672-Tumor Cells, Cultured,
pubmed-meshheading:12845672-Tyrosine,
pubmed-meshheading:12845672-beta-Lactamases
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pubmed:year |
2003
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pubmed:articleTitle |
The HGF/SF antagonist NK4 reverses fibroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo.
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pubmed:affiliation |
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, Wales, UK. daviesg11@cf.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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