Novel xenograft model expressing human hepatocyte growth factor shows ligand-dependent growth of c-Met-expressing tumors Journal Article
| Authors: | Francone, T. D.; Landmann, R. G.; Chen, C. T.; Sun, M. Y.; Kuntz, E. J.; Zeng, Z.; DeMatteo, R. P.; Paty, P. B.; Weiser, M. R. |
| Article Title: | Novel xenograft model expressing human hepatocyte growth factor shows ligand-dependent growth of c-Met-expressing tumors |
| Abstract: | c-Met, a receptor tyrosine kinase responsible for cellular migration, invasion, and proliferation, is overexpressed in human cancers. Although ligand-independent c-Met activation has been described, the majority of tumors are ligand dependent and rely on binding of hepatocyte growth factor (HGF) for receptor activation. Both receptor and ligand are attractive therapeutic targets; however, preclinical models are limited because murine HGF does not activate human c-Met. The goal of this study was to develop a xenograft model in which human HGF (hHGF) is produced in a controllable fashion in the mouse. Severe combined immunodeficient mice were treated with adenovirus encoding the hHGF transgene (Ad-hHGF) via tail vein injection, and transgene expression was determined by the presence of hHGF mRNA in mouse tissue and hHGF in serum. Ad-hHGF administration to severe combined immunodeficient mice resulted in hHGF production that was (a) dependent on quantity of virus delivered; (b) biologically active, resulting in liver hypertrophy; and (c) sustainable over 40 days. In this model, the ligand-dependent human tumor cell line SW1417 showed enhanced tumor growth, whereas the ligand-independent cell lines SW480 and GTL-16 showed no augmented tumor growth. This novel xenograft model is ideal for investigating c-Met/HGF - dependent human tumor progression and for evaluating c-Met targeted therapy. Copyright © 2007 American Association for Cancer Research. |
| Keywords: | controlled study; protein expression; human cell; nonhuman; neoplasms; cell proliferation; protein blood level; mouse; animals; mice; animal tissue; gene expression; protein targeting; animal experiment; animal model; tumor xenograft; mice, scid; xenograft model antitumor assays; cell line, tumor; phosphorylation; transgenic mouse; viral gene delivery system; scatter factor; gene expression regulation, neoplastic; messenger rna; tumor cell line; ligand; transplantation, heterologous; ligands; tumor model; adenovirus vector; tumor growth; colon carcinoma; scid mouse; transgenes; liver hypertrophy; adenoviridae; scatter factor receptor; proto-oncogene proteins c-met; hepatocyte growth factor |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-04-01 |
| Start Page: | 1460 |
| End Page: | 1466 |
| Language: | English |
| DOI: | 10.1158/1535-7163.mct-06-0466 |
| PUBMED: | 17431125 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: MCTOC" - "Source: Scopus" |
