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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-7-7
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
348-54
pubmed:dateRevised
2009-11-19
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
pubmed:year
2003
pubmed:articleTitle
The HGF/SF antagonist NK4 reverses fibroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo.
pubmed:affiliation
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, Wales, UK. daviesg11@cf.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't