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http://purl.uniprot.org/citations/14519655http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14519655http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Hepatocyte growth factor/scatter factor (HGF/SF) is known to increase the invasiveness and migration of cancer cells in vitro and induce angiogenesis. This study examined if inhibition of HGF/SF receptor expression by cancer cells and HGF/SF expression by stromal fibroblasts affects the growth of mammary cancer.

Experimental design

Transgenes encoding ribozymes to specifically target human HGF/SF receptor (pLXSN-MET) or HGF/SF (pLXSN-HGF) were constructed using a pLXSN retroviral vector. Human mammary cancer cells MDA MB 231 was transduced with pLXSN-MET (MDA(+/+)). A human fibroblast cell line MRC5, which produces bioactive HGF/SF, was transduced with pLXSN-HGF (MRC5(+/+)). These cells were used in a nude mice breast tumor model.

Results

HGF receptor in MDA(+/+) cells and HGF in MRC5(+/+)cells were successfully removed with respective ribozymes as shown by reverse transcription-PCR and Western blotting, respectively. MDA(+/+) was found to have reduced invasiveness when stimulated with HGF/SF. MRC5(+/+) exhibited a significant reduction in HGF/SF production. When injected into athymic nude mice, MDA(+/+) exhibited a slower rate of growth, compared with the wild type (MDA(-/-)), and the cells transduced with control viral vector (MDA(+/-)). The growth of MDA(-/-) tumor was significantly enhanced when coimplanted with wild-type MRC5 (MRC5(-/-)), and the stimulatory effect was reduced when MRC5(+/+) cells were coimplanted instead of MRC5(-/-). The reduction of tumor growth was accompanied by reduction of angiogenesis, as demonstrated by the staining of VE-cadherin in primary tumor tissues.

Conclusions

Retroviral ribozyme transgenes targeting HGF/SF in fibroblasts or its receptor cMET in mammary cancer cells can reduce the growth of mammary cancer and associated angiogenesis by inhibiting paracrine stromal-tumor cell interactions."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Davies G."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Jiang W.G."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Mansel R.E."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Lane J."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Parr C."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Martin T.A."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Laterra J."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Abounader R."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Grimshaw D."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/author"Watkins G."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/pages"4274-4281"xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/title"Reduction of stromal fibroblast-induced mammary tumor growth, by retroviral ribozyme transgenes to hepatocyte growth factor/scatter factor and its receptor, c-MET."xsd:string
http://purl.uniprot.org/citations/14519655http://purl.uniprot.org/core/volume"9"xsd:string
http://purl.uniprot.org/citations/14519655http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/14519655
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