Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/6672
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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 1532-1827 |
Statement of Responsibility: | 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 |
DOI: | 10.1038/sj.bjc.6601021 |
Published version: | http://dx.doi.org/10.1038/sj.bjc.6601021 |
Appears in Collections: | Aurora harvest 5 Orthopaedics and Trauma publications |
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