title: Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice.
abstract: 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.
authors.affiliation: Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A'Beckett Street, East Melbourne, 8006 Victoria, Australia.
authors.forename: Erika
authors.initials: E
authors.lastname: Cretney
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Moira
authors.initials: M
authors.lastname: Glaccum
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Peschon
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000556:secondary; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000276:immunology*; D009368:Neoplasm Transplantation; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008748:Methylcholanthrene