Resistance to TRAIL in mantle cell lymphoma cells is associated with the decreased expression of purine metabolism enzymes
| Autor: | Magdalena Klanova, Jiri Petrak, Lucie Lorkova, Ondrej Vit, Jan Zivny, Jana Pospisilova, Pavel Klener |
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| Rok vydání: | 2013 |
| Předmět: |
Proteomics
Cell Purine nucleoside phosphorylase Lymphoma Mantle-Cell Biology TNF-Related Apoptosis-Inducing Ligand Downregulation and upregulation hemic and lymphatic diseases Cell Line Tumor Genetics medicine Humans Electrophoresis Gel Two-Dimensional Purine metabolism Cell Death Cell Membrane Reproducibility of Results General Medicine Cell cycle medicine.disease Flow Cytometry Lymphoma Neoplasm Proteins Receptors TNF-Related Apoptosis-Inducing Ligand medicine.anatomical_structure Cell culture Drug Resistance Neoplasm Purines Immunology Cancer research Mantle cell lymphoma |
| Zdroj: | International journal of molecular medicine. 31(5) |
| ISSN: | 1791-244X |
| Popis: | Mantle cell lymphoma (MCL) is a rare aggressive type of B-cell non-Hodgkin's lymphoma. Response to chemo- therapy tends to be short and virtually all patients sooner or later relapse. The prognosis of relapsed patients is extremely poor. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered one of the novel experimental molecules with strong antitumor effects. TRAIL triggers extrinsic apop- totis in tumor cells by binding to TRAIL 'death receptors' on the cell surface. Recombinant TRAIL has shown promising pro-apoptotic effects in a variety of malignancies including lymphoma. However, as with other drugs, lymphoma cells can develop resistance to TRAIL. Therefore, the aim of this study was to identify the molecular mechanisms responsible for, and associated with TRAIL resistance in MCL cells. If identified, these features may be used as molecular targets for the effec- tive elimination of TRAIL-resistant lymphoma cells. From an established TRAIL-sensitive mantle cell lymphoma cell line (HBL-2) we derived a TRAIL-resistant HBL-2/R subclone. By TRAIL receptor analysis and differential proteomic analysis of HBL-2 and HBL-2/R cells we revealed a marked downregula- tion of all TRAIL receptors and, among others, the decreased expression of 3 key enzymes of purine nucleotide metabolism, namely purine nucleoside phosphorylase, adenine phosphoribo- syltransferase and inosine-5'-monophosphate dehydrogenase 2, in the resistant HBL-2/R cells. The downregulation of the 3 key enzymes of purine metabolism can have profound effects on nucleotide homeostasis in TRAIL-resistant lymphoma cells and can render such cells vulnerable to any further disruption of purine nucleotide metabolism. This pathway represents a 'weakness' of the TRAIL-resistant MCL cells and has potential as a therapeutic target for the selective elimination of such cells. |
| Databáze: | OpenAIRE |
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