Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas
| Autor: | Luc Xerri, Thierry Defrance, Françoise Birg, Elisabeth Devilard, Reda Bouabdallah, Jacques Hassoun, Fabienne Palmerini |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cytoplasm
Pathology medicine.medical_specialty ICAD Blotting Western Biology Pathology and Forensic Medicine immune system diseases hemic and lymphatic diseases medicine Humans Reed-Sternberg Cells Cell Nucleus B-Lymphocytes Caspase 8 Deoxyribonucleases Caspase 3 Lymphoma Non-Hodgkin Mantle zone Large cell Proteins Germinal center Germinal Center medicine.disease Marginal zone Hodgkin Disease Molecular biology Caspase 9 Neoplasm Proteins Non-Hodgkin's lymphoma Lymphoma Reed–Sternberg cell Case-Control Studies Caspases Apoptosis Regulatory Proteins |
| Zdroj: | The Journal of Pathology. 192:194-202 |
| ISSN: | 1096-9896 0022-3417 |
| Popis: | Lymphoma cells often display in vitro resistance to FAS-induced apoptosis, in which caspases act as crucial cell death effectors. Following FAS stimulation, caspase-8 activates caspase-3, which in turn activates the caspase-activated DNAse (CAD) by proteolysis of its inhibitor (ICAD). To investigate the mechanism of FAS resistance, the expression of caspase-8 was analysed by immunohistochemistry, together with that of the substrates caspase-3 and ICAD, in 52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's disease (HD), and eight benign lymphoid tissues. In benign tissues, caspase-8 was co-expressed with caspase-3 in the cytoplasm in germinal centre (GC) cells and was co-expressed with ICAD in the nuclei of the mantle and marginal zone cells. ICAD expression was weak or absent in GC cells. Cytoplasmic staining for both caspase-8 and caspase-3 was present in 11/12 cases of diffuse large cell B-NHL. Caspase-8 positivity was nuclear and cytoplasmic in 9/9 follicular NHLs, in 5/5 mantle cell NHLs and in 6/6 marginal zone NHLs. Five out of six peripheral T-cell NHLs expressed cytoplasmic caspase-8. Ten out of the 12 HD cases lacked significant cytoplasmic staining for caspase-3 and caspase-8 in the majority of Reed-Sternberg cells. All lymphoma cases exhibited predominant nuclear ICAD positivity. Subcellular fractionation analysis of three lymphoma samples and normal mantle zone cells confirmed that ICAD and caspase-8 were at least partly localized in the nucleus. These results show that the profile of caspase-8 expression is correlated with histological lymphoma subtypes; that caspase-8 is co-expressed with caspase-3 in GC cells and their neoplastic counterparts; that ICAD has an immunohistochemical nuclear localization in vivo; and that caspase-8 and ICAD can be co-expressed in the nuclei of mantle zone and marginal zone cells; their unexpected nuclear localization allows a reappraisal of the biochemical cascade of caspase activation. |
| Databáze: | OpenAIRE |
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