Abstract
Death ligands of the Tumor Necrosis Factor (TNF) family are known to induce apoptosis upon binding to their cognate receptors. However, the clinical utility of these cytokines as anticancer agents has been limited due to unacceptable toxicity. TRAIL is a recently isolated death ligand that possesses selective anti-tumor activity against a number of cancer cell lines without significant systemic toxicity. In this report we present evidence that cell lines derived from Ewing's Sarcoma (ES) are uniformly sensitive to TRAIL-mediated apoptosis. Furthermore, unlike TNF-α, treatment with TRAIL fails to induce the anti-apoptotic and pro-inflammatory NF-κB pathway in the ES cell lines. Our results suggest that TRAIL may prove to be a useful agent for the treatment of Ewing's sarcoma and related peripheral neuroectodermal tumors.
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References
Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z and Schwall RH. . 1999 J. Clin. Invest. 104: 155–162.
Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J and Hood L. . 1997 Immunity 7: 821–830.
Chaudhary PM, Jasmin A, Eby MT and Hood L. . 1999 Oncogene 18: 5738–5746.
de Alava E and Gerald WL. . 2000 J. Clin. Oncol. 18: 204–213.
Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA and Goodwin RG. . 1997 Immunity 7: 813–820.
French LE and Tschopp J. . 1999 Nat. Med. 5: 146–147.
Griffith TS, Chin WA, Jackson GC, Lynch DH and Kubin MZ. . 1998 J. Immunol. 161: 2833–2840.
Harbury PB, Kim PS and Alber T. . 1994 Nature 371: 80–83.
Hengere B and Mathe D. . 1996 Promega. Notes 58: 40–44.
Jeremias I and Debatin KM. . 1998 Eur. Cytokine. Netw. 9: 687–688.
Jeremias I, Kupatt C, Baumann B, Herr I, Wirth T and Debatin KM. . 1998 Blood 91: 4624–4631.
Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR and Strom SC. . 2000 Nat. Med. 6: 564–567.
Leverkus M, Neumann M, Mengling T, Rauch CT, Brocker EB, Krammer PH and Walczak H. . 2000 Cancer. Res. 60: 553–559.
Marsters SA, Pitti RM, Donahue CJ, Ruppert S, Bauer KD and Ashkenazi A. . 1996 Curr. Biol. 6: 750–752.
Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, Grooten J, Fiers W and Vandenabeele P. . 1998 J. Exp. Med. 187: 1477–1485.
Vercammen D, Vandenabeele P, Beyaert R, Declercq W and Fiers W. . 1997 Cytokine 9: 801–808.
Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG and Rauch CT. . 1997 EMBO J. 16: 5386–5397.
Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC and Lynch DH. . 1999 Nat. Med. 5: 157–163.
Acknowledgements
We thank Drs Lee Hellman and John Minna for various cell lines used in the present study. This work was supported by a grant from the Nearburg Family Foundation (to PM Chaudhary).
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Kumar, A., Jasmin, A., Eby, M. et al. Cytotoxicity of Tumor Necrosis Factor related apoptosis-inducing ligand towards Ewing's sarcoma cell lines. Oncogene 20, 1010–1014 (2001). https://doi.org/10.1038/sj.onc.1204154
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DOI: https://doi.org/10.1038/sj.onc.1204154
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