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http://purl.uniprot.org/citations/19470725http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19470725http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

We determined hepatocyte growth factor (HGF) and c-Met expression and signaling in human head and neck squamous cell carcinoma (HNSCC) cells and primary tissues and tested the ability of c-Met tyrosine kinase inhibitors (TKI) to block HGF-induced biological signaling.

Experimental design

Expression and signaling were determined using immunoblotting, ELISA, and immunohistochemistry. Biological end points included wound healing, cell proliferation, and invasion. c-Met TKIs were tested for their ability to block HGF-induced signaling and biological effects in vitro and in xenografts established in nude mice.

Results

c-Met was expressed and functional in HNSCC cells. HGF was secreted by HNSCC tumor-derived fibroblasts, but not by HNSCC cells. Activation of c-Met promoted phosphorylation of AKT and mitogen-activated protein kinase as well as release of the inflammatory cytokine interleukin-8. Cell growth and wound healing were also stimulated by HGF. c-Met TKIs blocked HGF-induced signaling, interleukin-8 release, and wound healing. Enhanced invasion of HNSCC cells induced by the presence of tumor-derived fibroblasts was completely blocked with a HGF-neutralizing antibody. PF-2341066, a c-Met TKI, caused a 50% inhibition of HNSCC tumor growth in vivo with decreased proliferation and increased apoptosis within the tumors. In HNSCC tumor tissues, both HGF and c-Met protein were increased compared with expression in normal mucosa.

Conclusions

These results show that HGF acts mainly as a paracrine factor in HNSCC cells, the HGF/c-Met pathway is frequently up-regulated and functional in HNSCC, and a clinically relevant c-Met TKI shows antitumor activity in vivo. Blocking the HGF/c-Met pathway may be clinically useful for the treatment of HNSCC."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-08-3252"xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Suzuki S."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Ferris R.L."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Thomas S.M."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Egloff A.M."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Morgan S."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Lerner E.C."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Siegfried J.M."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Grandis J.R."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Stabile L.P."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Knowles L.M."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Seethala R.R."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Gubish C.T."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Rothstein M.E."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/author"Quesnelle K.M."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/pages"3740-3750"xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/title"HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer."xsd:string
http://purl.uniprot.org/citations/19470725http://purl.uniprot.org/core/volume"15"xsd:string
http://purl.uniprot.org/citations/19470725http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19470725
http://purl.uniprot.org/citations/19470725http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19470725
http://purl.uniprot.org/uniprot/#_C9WSJ3-mappedCitation-19470725http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19470725
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