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Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis.
Cell Death Differ. 2001 May; 8(5):506-14.CD

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-gamma 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.

Authors+Show Affiliations

Children's Hospital of the Albert-Ludwigs-University, Freiburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11423911

Citation

Kontny, H U., et al. "Sensitivity of Ewing's Sarcoma to TRAIL-induced Apoptosis." Cell Death and Differentiation, vol. 8, no. 5, 2001, pp. 506-14.
Kontny HU, Hämmerle K, Klein R, et al. Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis. Cell Death Differ. 2001;8(5):506-14.
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), 506-14.
Kontny HU, et al. Sensitivity of Ewing's Sarcoma to TRAIL-induced Apoptosis. Cell Death Differ. 2001;8(5):506-14. PubMed PMID: 11423911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis. AU - Kontny,H U, AU - Hämmerle,K, AU - Klein,R, AU - Shayan,P, AU - Mackall,C L, AU - Niemeyer,C M, PY - 2000/03/14/received PY - 2000/10/05/revised PY - 2000/12/29/accepted PY - 2001/6/26/pubmed PY - 2001/8/10/medline PY - 2001/6/26/entrez SP - 506 EP - 14 JF - Cell death and differentiation JO - Cell Death Differ VL - 8 IS - 5 N2 - 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-gamma 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. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/11423911/Sensitivity_of_Ewing's_sarcoma_to_TRAIL_induced_apoptosis_ L2 - https://doi.org/10.1038/sj.cdd.4400836 DB - PRIME DP - Unbound Medicine ER -