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Departments of
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Immunobiology,
Protein Chemistry,
Biochemistry,
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Molecular Biology, and
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Hybridoma, Immunex Corporation, Seattle, WA 98101
mAbs were generated against the extracellular domain of the four known TNF-related apoptosis-inducing ligand (TRAIL) receptors and tested on a panel of human melanoma cell lines. The specificity of the mAb permitted a precise evaluation of the TRAIL receptors that induce apoptosis (TRAIL-R1 and -R2) compared with the TRAIL receptors that potentially regulate TRAIL-mediated apoptosis (TRAIL-R3 and -R4). Immobilized anti-TRAIL-R1 or -R2 mAbs were cytotoxic to TRAIL-sensitive tumor cells, whereas tumor cells resistant to recombinant TRAIL were also resistant to these mAbs and only became sensitive when cultured with actinomycin D. The anti-TRAIL-R1 and -R2 mAb-induced death was characterized by the activation of intracellular caspases, which could be blocked by carbobenzyloxy-Val-Ala-Asp (OMe) fluoromethyl ketone (zVAD-fmk) and carbobenzyloxy-Ile-Glu(OMe)-Thr-Asp (OMe) fluoromethyl ketone (zIETD-fmk). When used in solution, one of the anti-TRAIL-R2 mAbs was capable of blocking leucine zipper-human TRAIL binding to TRAIL-R2-expressing cells and prevented TRAIL-induced death of these cells, whereas two of the anti-TRAIL-R1 mAbs could inhibit leucine zipper-human TRAIL binding to TRAIL-R1:Fc. Furthermore, use of the blocking anti-TRAIL-R2 mAb allowed us to demonstrate that the signals transduced through either TRAIL-R1 or TRAIL-R2 were necessary and sufficient to mediate cell death. In contrast, the expression of TRAIL-R3 or TRAIL-R4 did not appear to be a significant factor in determining the resistance or sensitivity of these tumor target cells to the effects of TRAIL.
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T. S. Griffith, J. M. Fialkov, D. L. Scott, T. Azuhata, R. D. Williams, N. R. Wall, D. C. Altieri, and A. D. Sandler Induction and Regulation of Tumor Necrosis Factor-related Apoptosis-inducing Ligand/Apo-2 Ligand-mediated Apoptosis in Renal Cell Carcinoma Cancer Res., June 1, 2002; 62(11): 3093 - 3099. [Abstract] [Full Text] [PDF]
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J. J. Lum, A. A. Pilon, J. Sanchez-Dardon, B. N. Phenix, J. E. Kim, J. Mihowich, K. Jamison, N. Hawley-Foss, D. H. Lynch, and A. D. Badley Induction of Cell Death in Human Immunodeficiency Virus-Infected Macrophages and Resting Memory CD4 T Cells by TRAIL/Apo2L J. Virol., November 15, 2001; 75(22): 11128 - 11136. [Abstract] [Full Text] [PDF]
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 D. Y. Zang, R. G. Goodwin, M. R. Loken, E. Bryant, and H. J. Deeg Expression of tumor necrosis factor-related apoptosis-inducing ligand, Apo2L, and its receptors in myelodysplastic syndrome: effects on in vitro hemopoiesis Blood, November 15, 2001; 98(10): 3058 - 3065. [Abstract] [Full Text] [PDF]
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P. Secchiero, P. Mirandola, D. Zella, C. Celeghini, A. Gonelli, M. Vitale, S. Capitani, and G. Zauli Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4+ T cells Blood, October 15, 2001; 98(8): 2474 - 2481. [Abstract] [Full Text] [PDF]
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A. E. Tollefson, K. Toth, K. Doronin, M. Kuppuswamy, O. A. Doronina, D. L. Lichtenstein, T. W. Hermiston, C. A. Smith, and W. S. M. Wold Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins J. Virol., October 1, 2001; 75(19): 8875 - 8887. [Abstract] [Full Text] [PDF]
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X. D. Zhang, X. Y. Zhang, C. P. Gray, T. Nguyen, and P. Hersey Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis of Human Melanoma Is Regulated by Smac/DIABLO Release from Mitochondria Cancer Res., October 1, 2001; 61(19): 7339 - 7348. [Abstract] [Full Text] [PDF]
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C. S. Mitsiades, S. P. Treon, N. Mitsiades, Y. Shima, P. Richardson, R. Schlossman, T. Hideshima, and K. C. Anderson TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications Blood, August 1, 2001; 98(3): 795 - 804. [Abstract] [Full Text] [PDF]
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A. V. Franco, X. D. Zhang, E. Van Berkel, J. E. Sanders, X. Y. Zhang, W. D. Thomas, T. Nguyen, and P. Hersey The Role of NF-{{kappa}}B in TNF-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis of Melanoma Cells J. Immunol., May 1, 2001; 166(9): 5337 - 5345. [Abstract] [Full Text] [PDF]
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R. Di Pietro, P. Secchiero, R. Rana, D. Gibellini, G. Visani, K. Bemis, L. Zamai, S. Miscia, and G. Zauli Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity by selective up-regulation of TRAIL-R1 Blood, May 1, 2001; 97(9): 2596 - 2603. [Abstract] [Full Text] [PDF]
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A. Chuntharapai, K. Dodge, K. Grimmer, K. Schroeder, S. A. Marsters, H. Koeppen, A. Ashkenazi, and K. J. Kim Isotype-Dependent Inhibition of Tumor Growth In Vivo by Monoclonal Antibodies to Death Receptor 4 J. Immunol., April 15, 2001; 166(8): 4891 - 4898. [Abstract] [Full Text] [PDF]
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R. D. Pettersen, G. Bernard, M. K. Olafsen, M. Pourtein, and S. O. Lie CD99 Signals Caspase-Independent T Cell Death J. Immunol., April 15, 2001; 166(8): 4931 - 4942. [Abstract] [Full Text] [PDF]
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 E. H. Alexander, J. L. Bento, F. M. Hughes Jr., I. Marriott, M. C. Hudson, and K. L. Bost Staphylococcus aureus and Salmonella enterica Serovar Dublin Induce Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression by Normal Mouse and Human Osteoblasts Infect. Immun., March 1, 2001; 69(3): 1581 - 1586. [Abstract] [Full Text] [PDF]
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N. Mitsiades, V. Poulaki, C. Mitsiades, and M. Tsokos Ewing's Sarcoma Family Tumors Are Sensitive to Tumor Necrosis Factor-related Apoptosis-inducing Ligand and Express Death Receptor 4 and Death Receptor 5 Cancer Res., March 1, 2001; 61(6): 2704 - 2712. [Abstract] [Full Text]
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H. Matsuzaki, B. M. Schmied, A. Ulrich, J. Standop, M. B. Schneider, S. K. Batra, K. S. Picha, and P. M. Pour Combination of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Actinomycin D Induces Apoptosis Even in TRAIL-resistant Human Pancreatic Cancer Cells Clin. Cancer Res., February 1, 2001; 7(2): 407 - 414. [Abstract] [Full Text]
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W. D. Thomas, X. D. Zhang, A. V. Franco, T. Nguyen, and P. Hersey TNF-Related Apoptosis-Inducing Ligand-Induced Apoptosis of Melanoma Is Associated with Changes in Mitochondrial Membrane Potential and Perinuclear Clustering of Mitochondria J. Immunol., November 15, 2000; 165(10): 5612 - 5620. [Abstract] [Full Text] [PDF]
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L. Zamai, P. Secchiero, S. Pierpaoli, A. Bassini, S. Papa, E. S. Alnemri, L. Guidotti, M. Vitale, and G. Zauli TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis Blood, June 15, 2000; 95(12): 3716 - 3724. [Abstract] [Full Text] [PDF]
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H. Walczak, A. Bouchon, H. Stahl, and P. H. Krammer Tumor Necrosis Factor-related Apoptosis-inducing Ligand Retains Its Apoptosis-inducing Capacity on Bcl-2- or Bcl-xL-overexpressing Chemotherapy-resistant Tumor Cells Cancer Res., June 1, 2000; 60(11): 3051 - 3057. [Abstract] [Full Text] [PDF]
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M. Giovarelli, P. Musiani, G. Garotta, R. Ebner, E. Di Carlo, Y. Kim, P. Cappello, L. Rigamonti, P. Bernabei, F. Novelli, et al. A ""Stealth Effect"": Adenocarcinoma Cells Engineered to Express TRAIL Elude Tumor-Specific and Allogeneic T Cell Reactions J. Immunol., November 1, 1999; 163(9): 4886 - 4893. [Abstract] [Full Text] [PDF]
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 N. A. Fanger, C. R. Maliszewski, K. Schooley, and T. S. Griffith Human Dendritic Cells Mediate Cellular Apoptosis via Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) J. Exp. Med., October 18, 1999; 190(8): 1155 - 1164. [Abstract] [Full Text] [PDF]
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L. M. Sedger, D. M. Shows, R. A. Blanton, J. J. Peschon, R. G. Goodwin, D. Cosman, and S. R. Wiley IFN-{gamma} Mediates a Novel Antiviral Activity Through Dynamic Modulation of TRAIL and TRAIL Receptor Expression J. Immunol., July 15, 1999; 163(2): 920 - 926. [Abstract] [Full Text] [PDF]
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X. D. Zhang, A. Franco, K. Myers, C. Gray, T. Nguyen, and P. Hersey Relation of TNF-related Apoptosis-inducing Ligand (TRAIL) Receptor and FLICE-inhibitory Protein Expression to TRAIL-induced Apoptosis of Melanoma Cancer Res., June 1, 1999; 59(11): 2747 - 2753. [Abstract] [Full Text] [PDF]
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C. A. Benedict, P. S. Norris, T. I. Prigozy, J.-L. Bodmer, J. A. Mahr, C. T. Garnett, F. Martinon, J. Tschopp, L. R. Gooding, and C. F. Ware Three Adenovirus E3 Proteins Cooperate to Evade Apoptosis by Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor-1 and -2 J. Biol. Chem., January 26, 2001; 276(5): 3270 - 3278. [Abstract] [Full Text] [PDF]
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A. Truneh, S. Sharma, C. Silverman, S. Khandekar, M. P. Reddy, K. C. Deen, M. M. Mclaughlin, S. M. Srinivasula, G. P. Livi, L. A. Marshall, et al. Temperature-sensitive Differential Affinity of TRAIL for Its Receptors. DR5 IS THE HIGHEST AFFINITY RECEPTOR J. Biol. Chem., July 21, 2000; 275(30): 23319 - 23325. [Abstract] [Full Text] [PDF]
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