| Interferon-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis by up-regulating Fas receptors and caspase-8. | |
| | |
MedLine Citation:
|
PMID: 15390286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Osteosarcoma is the third most frequent neoplasm in adolescents. Although chemotherapy, frequently used in pre- and post-operative settings, has resulted in significant improvement in disease-free survival, some patients show little sensitivity to chemotherapy and alternative therapeutic strategies are needed. Because the Fas ligand/Fas receptor (CD95, APO-1) apoptosis pathway is a potential therapeutic target in osteosarcomas, we examined the effect of IFN-gamma on Fas-induced apoptosis in four osteosarcoma cell lines. PROCEDURE AND RESULTS: As measured by flow cytometry, all cell lines expressed cell surface IFN-gamma receptors, and when cultured for 2 days in the presence of IFN-gamma, all cell lines exhibited a significant increase in expression of Fas receptors. By flow cytometric detection of intracellular fragmented DNA as a marker of apoptosis, all cell lines cultured with either IFN-gamma or anti-Fas antibody (clone CH-11) alone showed only moderate apoptosis, whereas significantly high levels of apoptosis occurred in cells cultured with both IFN-gamma and CH-11. Western blotting analysis also revealed that IFN-gamma caused up-regulation of caspase-8 in all cell lines, but no change in Fas-associated death domain protein (FADD/MORT1) or caspase-3. Both caspase-8 and caspase-3 were activated when apoptosis was induced with both IFN-gamma and CH-11. Addition to cultures of z-IETD-fmk, an inhibitor of caspase-8, significantly blocked this apoptosis. CONCLUSIONS: IFN-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis through up-regulation of Fas receptor and caspase-8. Combined immunotherapy with IFN-gamma and either anti-Fas monoclonal antibody or cytotoxic T cells that bear Fas ligand might be a useful adjunctive therapy for patients with osteosarcoma. |
| | |
Authors:
|
Hiroto Inaba; Maria Glibetic; Steven Buck; Yaddanapudi Ravindranath; Joseph Kaplan |
Related Documents
:
|
9341746 - Unmethylated cpg motifs protect murine b lymphocytes against fas-mediated apoptosis. 12543166 - Sensitization of head and neck squamous cell carcinoma cells to fas-mediated apoptosis ... 9478956 - Caspase-dependent ceramide production in fas- and hla class i-mediated peripheral t cel... 9402086 - Cytokines and fas regulate apoptosis in murine renal interstitial fibroblasts. 15286806 - The anaphylatoxin c3a downregulates the th2 response to epicutaneously introduced antigen. 23653226 - Mucopolysaccharide diseases: a complex interplay between neuroinflammation, microglial ... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Pediatric blood & cancer Volume: 43 ISSN: 1545-5009 ISO Abbreviation: Pediatr Blood Cancer Publication Date: 2004 Dec |
Date Detail:
|
Created Date: 2004-11-03 Completed Date: 2005-01-18 Revised Date: 2009-01-12 |
Medline Journal Info:
|
Nlm Unique ID: 101186624 Medline TA: Pediatr Blood Cancer Country: United States |
Other Details:
|
Languages: eng Pagination: 729-36 Citation Subset: IM |
Copyright Information:
|
2004 Wiley-Liss, Inc. |
Affiliation:
|
Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, Michigan, USA. hiroto.inaba@stjude.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adaptor Proteins, Signal Transducing
/
analysis Antigens, CD95 / genetics*, physiology Apoptosis / drug effects* Caspase 3 Caspase 8 Caspases / analysis, genetics* Cell Line, Tumor Drug Synergism Fas-Associated Death Domain Protein Flow Cytometry Humans Interferon-gamma / pharmacology* Osteosarcoma / pathology* Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
|
0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD95; 0/FADD protein, human; 0/Fas-Associated Death Domain Protein; 82115-62-6/Interferon-gamma; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Differences in pediatric oncologists' estimates of curability and treatment recommendations for pati...
Next Document: Intracranial relapse in Wilms tumor patients.