Resistance to TRAIL in mantle cell lymphoma cells is associated with the decreased expression of purine metabolism enzymes
Jazyk angličtina Země Řecko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23503700
DOI
10.3892/ijmm.2013.1302
Knihovny.cz E-zdroje
- MeSH
- 2D gelová elektroforéza MeSH
- buněčná membrána metabolismus MeSH
- buněčná smrt účinky léků MeSH
- chemorezistence účinky léků MeSH
- lidé MeSH
- lymfom z plášťových buněk enzymologie patologie MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny metabolismus MeSH
- protein TRAIL farmakologie MeSH
- proteomika MeSH
- průtoková cytometrie MeSH
- puriny metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- TRAIL receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové proteiny MeSH
- protein TRAIL MeSH
- purine MeSH Prohlížeč
- puriny MeSH
- TRAIL receptory MeSH
Mantle cell lymphoma (MCL) is a rare aggressive type of B-cell non-Hodgkin's lymphoma. Response to chemotherapy 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 apoptotis 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 effective 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 downregulation of all TRAIL receptors and, among others, the decreased expression of 3 key enzymes of purine nucleotide metabolism, namely purine nucleoside phosphorylase, adenine phosphoribosyltransferase 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.
Citace poskytuje Crossref.org
