TNF-related apoptosis inducing ligand (TRAIL) and its receptors in tumor surveillance and cancer therapy.
TNF-related apoptosis-inducing ligand (TRAIL/APO-2L) is a typical member of the TNF ligand family that induces apoptosis by activating the death receptors TRAIL-R1 and TRAIL-R2. TRAIL has attracted great attention in recent years as a promising anti cancer reagent because recombinant soluble TRAIL derivatives induce apoptosis in a broad range of tumor cells but not or only rarely in non-transformed cells. In this review we will address the putative role of TRAIL in cancer treatment in the light of the emerging importance of TRAIL in tumor surveillance and discuss the molecular basis of the cooperation of TRAIL and chemotherapeutic drugs. In particular, we debate controversial data in the literature concerning the cytotoxicity of different TRAIL derivatives on primary human cells.
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany. harald.wajant@po.uni-stuttgart.de
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Wajant
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Pfizenmaier
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Scheurich
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007157:Immunologic Surveillance / Q000187:drug effects* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha