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Type: Journal article
Title: Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy
Author: Bouralexis, S.
Findlay, D.
Atkins, G.
Labrinidis, A.
Hay, S.
Evdokiou, A.
Citation: British Journal of Cancer, 2003; 89(1):206-214
Publisher: Churchill Livingstone
Issue Date: 2003
ISSN: 0007-0920
Statement of
S Bouralexis, D M Findlay, G J Atkins, A Labrinidis, S Hay & A Evdokiou
Abstract: Apo2 ligand (Apo2L, also known as TRAIL) is a member of the tumour necrosis factor (TNF) family of cytokines that selectively induces the death of cancer cells, but not of normal cells. We observed that recombinant Apo2L/TRAIL was proapoptotic in early-passage BTK-143 osteogenic sarcoma cells, inducing 80% cell death during a 24 h treatment period. Apo2L/TRAIL-induced apoptosis was blocked by caspase inhibition. With increasing passage in culture, BTK-143 cells became progressively resistant to the apoptotic effects of Apo2L/TRAIL . RNA and flow cytometric analysis demonstrated that resistance to Apo2L/TRAIL was paralleled by progressive acquisition of the decoy receptor, DcR2. Blocking of DcR2 function with a specific anti-DcR2 antibody restored sensitivity to Apo2L/TRAIL in a dose-dependent manner. Importantly, treatment of resistant cells with the chemotherapeutic agents doxorubicin, cisplatin and etoposide reversed the resistance to Apo2L/TRAIL, which was associated with drug-induced upregulation of mRNA encoding the death receptors DR4 and DR5. BTK-143 cells thus represent a useful model system to investigate both the mechanisms of acquisition of resistance of tumour cells to Apo2L/TRAIL and the use of conventional drugs and novel agents to overcome resistance to Apo2L/TRAIL.
Keywords: DcR2; Apo2L/TRAIL; osteosarcoma; resistance; chemotherapy; apoptosis
Description: © 2003 Cancer Research UK
RMID: 0020030110
DOI: 10.1038/sj.bjc.6601021
Appears in Collections:Orthopaedics and Trauma publications

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