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Enhanced growth of human met-expressing xenografts in a new strain of immunocompromised mice transgenic for human hepatocyte growth factor/scatter factor

Oncogene volume 24, pages 101–106 (2005)Cite this article

Abstract

Downstream signaling that results from the interaction of hepatocyte growth factor/scatter factor (HGF/SF) with the receptor tyrosine kinase Met plays critical roles in tumor development, progression, and metastasis. This ligand–receptor pair is an attractive target for new diagnostic and therapeutic agents, preclinical development of which requires suitable animal models. The growth of heterotopic and orthotopic Met-expressing human tumor xenografts in conventional strains of immunocompromised mice inadequately replicates the paracrine stimulation by human HGF/SF (hHGF/SF) that occurs in humans with cancer. We have therefore generated a mouse strain transgenic for hHGF/SF (designated hHGF-Tg) on a severe combined immunodeficiency (SCID) background. We report here that the presence of ectopically expressed hHGF/SF ligand significantly enhances growth of heterotopic subcutaneous xenografts derived from human Met-expressing cancer cells, including the lines SK-LMS-1 (human leiomyosarcoma), U118 (human glioblastoma), and DU145 (human prostate carcinoma), but not that of M14-Mel xenografts (human melanoma that expresses insignificant levels of Met). Our results indicate that ectopic hHGF/SF can specifically activate Met in human tumor xenografts. This new hHGF-Tg strain of mice should provide a powerful tool for evaluating drugs and diagnostic agents that target the various pathways influenced by Met activity.

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Acknowledgements

We thank Bryn Eagleson and the Van Andel Research Institute vivarium staff for their expert care of transgenic and nontransgenic mice, and Michelle Reed for the manuscript preparation. This work is supported in part by funding from the Michigan Life Sciences Corridor (MLSC) and by the generosity of the Jay and Betty Van Andel Foundation.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA

    Yu-Wen Zhang, Yanli Su, Nathan Lanning, Margaret Gustafson, Nariyoshi Shinomiya, Rick Hay & George F Vande Woude

  2. Laboratory of Antibody Technology, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA

    Ping Zhao & Brian Cao

  3. Sheba Medical Center, Tel Aviv, Israel

    Galia Tsarfaty

  4. Vita Genomics, Inc., Taipei, Taiwan

    Ling-Mei Wang

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  1. Yu-Wen Zhang
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Correspondence to George F Vande Woude.

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Zhang, YW., Su, Y., Lanning, N. et al. Enhanced growth of human met-expressing xenografts in a new strain of immunocompromised mice transgenic for human hepatocyte growth factor/scatter factor. Oncogene 24, 101–106 (2005). https://doi.org/10.1038/sj.onc.1208181

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