Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis

H. U. Kontny, K. Hämmerle, R. Klein, P. Shayan, C. L. Mackall, C. M. Niemeyer

Research output: Contribution to journalArticle

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to kill transformed cells. We have studied the expression and functionality of the TRAIL apoptotic pathway in Ewing's sarcoma. We demonstrate that tumors from patients with Ewing's sarcoma express receptors TRAIL-R1 and -R2. Using a panel of nine Ewing's sarcoma cell lines TRAIL could induce apoptosis in seven cell lines. Preincubation with interferon-γ rendered the two resistant cell lines sensitive. TRAIL was the most potent inducer of apoptosis when compared to Fas ligand or TNF. TRAIL-mediated apoptosis could be inhibited by various caspase-inhibitors. No difference in the surface expression of TRAIL-receptors was observed between sensitive and resistant cell lines. Also, all cell lines had similar levels of expression of Flice-like inhibitory protein (FLIP) on immunoblot. However, the two resistant cell lines had only very low level expression of caspase 8 on RNA and protein level. In summary, we show that Ewing's sarcoma expresses receptors for TRAIL, and that cells are exquisitely sensitive to TRAIL-mediated apoptosis. These results may warrant clinical trials with TRAIL in Ewing's sarcoma once the safety of TRAIL for humans has been established.

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalCell death and differentiation
Volume8
Issue number5
DOIs
StatePublished - Jun 11 2001

Keywords

  • Apoptosis
  • Caspase 8
  • Ewing's sarcoma
  • Interferon-γ
  • TRAIL

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Kontny, H. U., Hämmerle, K., Klein, R., Shayan, P., Mackall, C. L., & Niemeyer, C. M. (2001). Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis. Cell death and differentiation, 8(5), 506-514. https://doi.org/10.1038/sj.cdd.4400836