Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Leithner, K; Stacher, E; Wurm, R; Ploner, F; Quehenberger, F; Wohlkoenig, C; Bálint, Z; Polachova, J; Olschewski, A; Samonigg, H; Popper, HH; Olschewski, H.
Nuclear and cytoplasmic death receptor 5 as prognostic factors in patients with non-small cell lung cancer treated with chemotherapy.
Lung Cancer. 2009; 65(1):98-104
Doi: 10.1016/j.lungcan.2008.10.015
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- Führende Autor*innen der Med Uni Graz
- Leithner Katharina
- Co-Autor*innen der Med Uni Graz
- Balint Zoltan
- Olschewski Andrea
- Olschewski Horst
- Ploner Ferdinand
- Polachova Jana
- Popper Helmuth
- Quehenberger Franz
- Samonigg Hellmut
- Stacher-Priehse Elvira
- Wohlkönig Christoph
- Wurm Robert
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- Abstract:
- Background: Death receptor 4 (DR4) and death receptor 5 (DR5) are tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) receptors that activate apoptosis via the extrinsic apoptosis pathway. DcR1 and DcR2 are decoy receptors for TRAIL that act antagonistically. Intracellular trafficking of TRAIL receptors has been described, but the role of the subcellular localization of TRAIL receptors in non-small cell lung cancer (NSCLC) progression is unclear. Methods: Expression and intracellular localization of pro-apoptotic and decoy TRAIL receptors were analyzed by immunohistochemistry in 50 samples of advanced or recurrent NSCLC. Using confocal microscopy, localization of TRAIL receptors was studied in NSCLC cell lines. Results: Cytoplasmic staining for all four TRAIL receptors was observed in the majority of samples. Nuclear staining was infrequent in the case of DR4 (12%) and DcR2 (8%), while DR5 and DcR1 were localized in the nucleus in 27% and 60% of samples. When overall survival was analyzed, cytoplasmic staining for DR5 in tumor cells (P = 0.025) and nuclear staining for DR5 in tumor cells (P = 0.007) were significant prognostic factors in univariate, as well as in multivariate analysis including clinicopathologic factors (P = 0.026 and 0.021, respectively). In A549, NCI-H358, and A427 NSCLC cells all four TRAIL receptors were found to be mainly located perinuclearly, but also in the nucleus. Conclusion: The study for the first time shows that TRAIL receptors are found in different intracellular compartments including the nucleus in NSCLC cells and that both nuclear and cytoplasmic DR5 might predict improved survival in patients with advanced NSCLC. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology
- Cell Line, Tumor -
- Cell Nucleus - metabolism
- Cytoplasm - metabolism
- Humans -
- Lung Neoplasms - drug therapy Lung Neoplasms - metabolism Lung Neoplasms - pathology
- Male -
- Microscopy, Confocal -
- Middle Aged -
- Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - metabolism Neoplasm Recurrence, Local - pathology
- Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism
- Subcellular Fractions - metabolism
- Tumor Markers, Biological - metabolism
- Find related publications in this database (Keywords)
- DR5
- Nuclear
- Apoptosis
- Non-small cell lung cancer
- Prognosis