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http://purl.uniprot.org/citations/32203220http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Stromal-tumour interactions facilitate pancreatic cancer (PC) progression. The hepatocyte growth factor (HGF)/c-MET pathway is upregulated in PC and mediates the interaction between cancer cells and stromal pancreatic stellate cells (PSCs). This study assessed the effect of HGF/c-MET inhibition plus gemcitabine (G) on the progression of advanced PC.

Methods

Orthotopic PC was produced by implantation of luciferase-tagged human cancer cells + human PSCs into mouse pancreas. Tumours were allowed to develop without treatment for 4 weeks. Mice were then treated for 6 weeks with one of the following: IgG, G, HGF inhibitor (Hi), c-MET inhibitor (Ci), Hi + Ci, Hi + G, Ci + G, or Hi + Ci + G.

Results

Bioluminescence imaging showed similar tumour sizes in all mice at the initiation of treatments. Triple therapy (Hi + Ci + G): (1) completely eliminated metastasis; (2) significantly reduced tumour size as assessed by bioluminescence and at necropsy; (3) significantly reduced proliferating cancer cell density and stem cell marker DCLK1 expression in tumours. In vitro 3D culture studies supported our in vivo findings.

Conclusion

Even at an advanced disease stage, a two-pronged approach, targeting (a) HGF/c-MET with relevant inhibitors and (b) cancer cells with chemotherapy, completely eliminated metastasis and significantly decreased tumour growth, suggesting that this is a promising treatment approach for PC."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.org/dc/terms/identifier"doi:10.1038/s41416-020-0782-1"xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Murakami T."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Xu Z."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Liu A.C."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Goldstein D."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Wilson J.S."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Perera C.J."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Apte M.V."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Pirola R.C."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Mekapogu A.R."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Pang T.C.Y."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/author"Pothula S.P."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/name"Br J Cancer"xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/pages"1486-1495"xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/title"Targeting the HGF/c-MET pathway in advanced pancreatic cancer: a key element of treatment that limits primary tumour growth and eliminates metastasis."xsd:string
http://purl.uniprot.org/citations/32203220http://purl.uniprot.org/core/volume"122"xsd:string
http://purl.uniprot.org/citations/32203220http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32203220
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http://purl.uniprot.org/uniprot/#_C9WSJ3-mappedCitation-32203220http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32203220
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