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Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.
Cancer Res. 2000 Aug 15; 60(16):4315-9.CR

Abstract

Human neuroblastoma (NB) is a highly heterogeneous childhood cancer that is aggressively malignant or can undergo spontaneous regression that may involve apoptosis. NB-derived cell lines were tested for their sensitivity to apoptosis induced by the tumor-selective ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Noninvasive S-type cell lines (NB cell lines of substrate adherent phenotype) are highly sensitive to TRAIL, whereas invasive N-type cell lines (NB cell lines of neuronal phenotype) are resistant. Whereas both S- and N-type cell lines express TRAIL-R2, FADD, and caspase-3 and -10, only S-type cells express caspase-8. Reduced levels of caspase-8 protein were also observed in a malignant stage IV NB tumor when compared with a benign ganglioneuroma. The caspase-8 gene is not deleted in either N-type NB cell lines or high-stage NB tumors. Caspase-8 expression can be induced by demethylation with 5-aza-2'deoxycytidine, which enhances sensitivity to TRAIL. Therefore, caspase-8 expression is silenced in malignant NB, which correlates to tumor severity and resistance to TRAIL-induced apoptosis.

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Authors+Show Affiliations

Hopkins-Donaldson S
Department of Pediatric Onco-Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Bodmer JL
No affiliation info available
Bourloud KB
No affiliation info available
Brognara CB
No affiliation info available
Tschopp J
No affiliation info available
Gross N
No affiliation info available

MeSH

AnimalsApoptosisApoptosis Regulatory ProteinsCaspase 3Caspase 8Caspase 9CaspasesEnzyme ActivationFas Ligand ProteinGanglioneuromaHumansImmunohistochemistryMembrane GlycoproteinsNeoplasm InvasivenessNeoplasm StagingNeural Cell Adhesion MoleculesNeuroblastomaPhenotypeRabbitsReceptors, Tumor Necrosis FactorRecombinant ProteinsTNF-Related Apoptosis-Inducing LigandTumor Cells, CulturedTumor Necrosis Factor-alpha

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10969767

Citation

Hopkins-Donaldson, S, et al. "Loss of Caspase-8 Expression in Highly Malignant Human Neuroblastoma Cells Correlates With Resistance to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis." Cancer Research, vol. 60, no. 16, 2000, pp. 4315-9.
Hopkins-Donaldson S, Bodmer JL, Bourloud KB, et al. Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res. 2000;60(16):4315-9.
Hopkins-Donaldson, S., Bodmer, J. L., Bourloud, K. B., Brognara, C. B., Tschopp, J., & Gross, N. (2000). Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Research, 60(16), 4315-9.
Hopkins-Donaldson S, et al. Loss of Caspase-8 Expression in Highly Malignant Human Neuroblastoma Cells Correlates With Resistance to Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis. Cancer Res. 2000 Aug 15;60(16):4315-9. PubMed PMID: 10969767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. AU - Hopkins-Donaldson,S, AU - Bodmer,J L, AU - Bourloud,K B, AU - Brognara,C B, AU - Tschopp,J, AU - Gross,N, PY - 2000/9/2/pubmed PY - 2000/9/19/medline PY - 2000/9/2/entrez SP - 4315 EP - 9 JF - Cancer research JO - Cancer Res VL - 60 IS - 16 N2 - Human neuroblastoma (NB) is a highly heterogeneous childhood cancer that is aggressively malignant or can undergo spontaneous regression that may involve apoptosis. NB-derived cell lines were tested for their sensitivity to apoptosis induced by the tumor-selective ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Noninvasive S-type cell lines (NB cell lines of substrate adherent phenotype) are highly sensitive to TRAIL, whereas invasive N-type cell lines (NB cell lines of neuronal phenotype) are resistant. Whereas both S- and N-type cell lines express TRAIL-R2, FADD, and caspase-3 and -10, only S-type cells express caspase-8. Reduced levels of caspase-8 protein were also observed in a malignant stage IV NB tumor when compared with a benign ganglioneuroma. The caspase-8 gene is not deleted in either N-type NB cell lines or high-stage NB tumors. Caspase-8 expression can be induced by demethylation with 5-aza-2'deoxycytidine, which enhances sensitivity to TRAIL. Therefore, caspase-8 expression is silenced in malignant NB, which correlates to tumor severity and resistance to TRAIL-induced apoptosis. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/10969767/Loss_of_caspase_8_expression_in_highly_malignant_human_neuroblastoma_cells_correlates_with_resistance_to_tumor_necrosis_factor_related_apoptosis_inducing_ligand_induced_apoptosis_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10969767 DB - PRIME DP - Unbound Medicine ER -
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