Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice.
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.
Cretney
Erika
E
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A'Beckett Street, East Melbourne, 8006 Victoria, Australia.
Takeda
Kazuyoshi
K
Yagita
Hideo
H
Glaccum
Moira
M
Peschon
Jacques J
JJ
Smyth
Mark J
MJ
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
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