An atypical caspase-independent death pathway for an immunogenic cancer cell line

Nicolas Larmonier, Claire Billerey, Cédric Rébé, Arnaud Parcellier, Monique Moutet, Annie Fromentin, Guido Kroemer, Carmen Garrido, Eric Solary, François Martin, Bernard Bonnotte

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6091-6100
Number of pages10
JournalOncogene
Volume21
Issue number39
DOIs
StatePublished - Sep 5 2002

Keywords

  • Apoptosis
  • Caspase-independent
  • Necrosis
  • Tumor immunology
  • z-VAD

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Larmonier, N., Billerey, C., Rébé, C., Parcellier, A., Moutet, M., Fromentin, A., Kroemer, G., Garrido, C., Solary, E., Martin, F., & Bonnotte, B. (2002). An atypical caspase-independent death pathway for an immunogenic cancer cell line. Oncogene, 21(39), 6091-6100. https://doi.org/10.1038/sj.onc.1205738