TRAIL: a mechanism of tumor surveillance in an immune privileged site.
TRAIL is a recently described member of the TNF superfamily. The ability of TRAIL to induce apoptosis in a large number of tumors has stimulated interest in TRAIL as a tumor therapeutic agent. Although TRAIL mRNA is expressed in a number of tissues, its functional significance to various organs is unknown. Because tumors rarely develop in the eye, we have examined this organ for functional TRAIL expression. Our analysis revealed that TRAIL mRNA and protein are constitutively expressed on numerous ocular structures, including the cornea and retina. More importantly, ocular tissue displays functional TRAIL as determined by in vitro killing of TRAIL-sensitive tumor cell lines. Previous studies have shown that ocular tissue also expresses functional Fas ligand (FasL). To assess the contribution of TRAIL and FasL for tumor cell killing in the eye, cell lines susceptible to both TRAIL and FasL were examined. The results show that ocular tissue kills via either ligand, suggesting a compensatory mechanism between TRAIL and FasL. Collectively, these results provide physiological evidence for ocular TRAIL expression, and suggest a role for this molecule in tumor surveillance in an immune privileged site.
Lee
Hae-Ock
HO
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Herndon
John M
JM
Barreiro
Ramon
R
Griffith
Thomas S
TS
Ferguson
Thomas A
TA
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D002455:Cell Division / Q000276:immunology; D003315:Cornea / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology; D008024:Ligands; D012515:Mast-Cell Sarcoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D006131:Growth Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor