An atypical caspase-independent death pathway for an immunogenic cancer cell line.
REGb cell line, a highly immunogenic tumor cell variant isolated from a rat colon cancer, yields regressive tumors when injected into syngeneic hosts. We previously demonstrated that REGb tumor immunogenicity was related to the capacity of releasing dead cells in vivo. Also, in vitro, REGb cell monolayers release dead cells, especially when cultured in serum-free medium. In the current study, we show that the release of dead cells results from an atypical death process associating features of necrosis and apoptosis. In spite of features considered as hallmarks of caspase-dependent apoptosis, including chromatin fragmentation and DNA oligonucleosomal cleavage, caspases are not activated and caspase inhibitors are ineffective to prevent REGb cell death. In contrast with a number of other types of cell death, the spontaneous death of REGb cells in culture depends on de novo protein synthesis as this death is blocked by low doses of the mRNA translation inhibitor cycloheximide. This unusual mode of cell death that associates necrotic and apoptotic features could provide optimal conditions for triggering a specific immune response.
INSERM U517, IFR 100, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
Nicolas
N
Larmonier
Claire
C
Billerey
Cédric
C
Rébé
Arnaud
A
Parcellier
Monique
M
Moutet
Annie
A
Fromentin
Guido
G
Kroemer
Carmen
C
Garrido
Eric
E
Solary
François
F
Martin
Bernard
B
Bonnotte
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003851:Deoxyribonucleases / Q000378:metabolism; D053222:Fas Ligand Protein; D005420:Flavoproteins / Q000378:metabolism; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D009707:Nucleosomes / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
C494831:Aifm1 protein, rat; D000590:Amino Acid Chloromethyl Ketones; D017304:Annexin A5; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D002843:Chromatin; D015853:Cysteine Proteinase Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D005420:Flavoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009707:Nucleosomes; D011500:Protein Synthesis Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003513:Cycloheximide; D003851:Deoxyribonucleases; D020169:Caspases