Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice

• Published in: The Journal of immunology (1950) 2002-02, Vol.168 (3), p.1356-1361
• Main Authors: Cretney, Erika, Takeda, Kazuyoshi, Yagita, Hideo, Glaccum, Moira, Peschon, Jacques J, Smyth, Mark J
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - immunology; Adenocarcinoma - secondary; Animals; Apoptosis Regulatory Proteins; Cell Division - genetics; Cell Division - immunology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - immunology; Cytotoxicity, Immunologic - genetics; Disease Susceptibility - immunology; Female; Fibrosarcoma - chemically induced; Fibrosarcoma - genetics; Fibrosarcoma - immunology; Fibrosarcoma - pathology; Gene Targeting; Genetic Predisposition to Disease; Kidney Neoplasms - genetics; Kidney Neoplasms - immunology; Killer Cells, Natural - immunology; Ligands; Liver Neoplasms - genetics; Liver Neoplasms - immunology; Liver Neoplasms - prevention & control; Liver Neoplasms - secondary; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Methylcholanthrene - toxicity; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Metastasis - genetics; Neoplasm Metastasis - immunology; Neoplasm Transplantation; TNF-Related Apoptosis-Inducing Ligand; TRAIL protein; Tumor Cells, Cultured - transplantation; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.3.1356

We have previously implicated TNF-related apoptosis-inducing ligand (TRAIL) in innate immune surveillance against tumor development. In this study, we describe the use of TRAIL gene-targeted mice to demonstrate the key role of TRAIL in suppressing tumor initiation and metastasis. Liver and spleen mononuclear cells from TRAIL gene-targeted mice were devoid of TRAIL expression and TRAIL-mediated cytotoxicity. TRAIL gene-targeted mice were more susceptible to experimental and spontaneous tumor metastasis, and the immunotherapeutic value of alpha-galactosylceramide was diminished in TRAIL gene-targeted mice. TRAIL gene-targeted mice were also more sensitive to the chemical carcinogen methylcholanthrene. These results substantiated TRAIL as an important natural effector molecule used in the host defense against transformed cells.