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

• Published in: Oncogene Vol. 24; no. 1; pp. 101 - 106
• Main Authors: ZHANG, Yu-Wen, SU, Yanli, VANDE WOUDE, George F, LANNING, Nathan, GUSTAFSON, Margaret, SHINOMIYA, Nariyoshi, PING ZHAO, CAO, Brian, TSARFATY, Galia, WANG, Ling-Mei, HAY, Rick
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 06.01.2005; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Cancer; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Fundamental and applied biological sciences. Psychology; Growth factors; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Humans; Immunocompromised Host - immunology; Kinases; Ligands; Mice; Mice, SCID; Mice, Transgenic; Molecular and cellular biology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-met; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Time Factors; Transgenic animals; Transplantation, Heterologous; Tumor Cells, Cultured; Tumors; United States > US; Grand Rapids Michigan; Human; Growth; Hepatocyte growth factor; Rodentia; tumor xenograft; Heterograft; Carcinogenesis; Immune deficiency; SCID; Strain; Vertebrata; Mammalia; Mouse; Tumor; transgenic; human HGF/SF; met
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208181

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.