Activation of caspase-8 triggers anoikis in human neuroblastoma cells
| Autor: | Rossana Tiberio, Maurizio Sabbatini, Claudio Santoro, Valentina Piffanelli, Chiarella Bozzo, Mario Cannas |
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| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Cellular differentiation Blotting Western Gene Expression Caspase 3 Antineoplastic Agents Tretinoin Cysteine Proteinase Inhibitors Caspase 8 Neuroblastoma Cell Line Tumor Humans Anoikis Caspase Analysis of Variance Extracellular Matrix Proteins Microscopy Confocal biology Cell adhesion molecule General Neuroscience Cell Differentiation General Medicine Cell biology Fibronectin Enzyme Activation Apoptosis biology.protein Cell Adhesion Molecules Oligopeptides |
| Zdroj: | Neuroscience research. 56(2) |
| ISSN: | 0168-0102 |
| Popis: | Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to grow, differentiate and survive. Many cell types including nervous cells undergo anoikis, a substrate-dependent apoptosis, when adhesion is impaired. Resistance of tumors to cytotoxic drugs is probably due to disturbed apoptosis programs. The proteolytic enzymes caspases are the main executioners of apoptosis. It was reported that caspase-8 expression is deficient in some neuroblastoma cells. We demonstrated that human neuroblastoma cell line SK-B-BE, differentiated with retinoic acid, expressed caspases 3, 8 and 9. Caspases 8 and 3, but not caspase-9 were activated in SK-N-BE cells cultured in suspension or on aspecific adhesive substrate. Cell positive to caspase-8 were classified into four stages, by morphometric and densitometric parameters. The use of the specific caspase-8 inhibitor Z-IETD-FMK dramatically reduced apoptosis, demonstrating that caspase-8 is the upstream initiator caspase during SK-N-BE cells anoikis. Among matrix proteins, type I collagen is the most effective and fibronectin the least in delaying anoikis. The activation of caspases 8 and 3 by unligated integrins was dependent on the state of neuronal differentiation, since the most differentiated cell was the most vulnerable to anoikis. These data show that activation of caspase-8 is specifically required to promote anoikis in SK-N-BE neuroblastoma cells. |
| Databáze: | OpenAIRE |
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