Immunosurveillance against tetraploidization-induced colon tumorigenesis

Alice Boilève, Laura Senovilla, Ilio Vitale, Delphine Lissa, Isabelle Martins, Didier Métivier, Stieneke Van Den Brink, Hans Clevers, Lorenzo Galluzzi, Maria Castedo, Guido Kroemer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Circumstantial evidence suggests that colon carcinogenesis can ensue the transient tetraploidization of (pre-)malignant cells. In line with this notion, the tumor suppressors APC and TP 53, both of which are frequently inactivated in colon cancer, inhibit tetraploidization in vitro and in vivo. Here, we show that - contrarily to their wild-type counterparts - Tp53-/- colonocytes are susceptible to drug-induced or spontaneous tetraploidization in vitro. Colon organoids generated from tetraploid Tp53-/- cells exhibit a close-to-normal morphology as compared to their diploid Tp53 -/- counterparts, yet the colonocytes constituting these organoids are characterized by an increased cell size and an elevated expression of the immunostimulatory protein calreticulin on the cell surface. The subcutaneous injection of tetraploid Tp53-/- colon organoids led to the generation of proliferating tumors in immunodeficient, but not immunocompetent, mice. Thus, tetraploid Tp53-/- colonocytes fail to survive in immunocompetent mice and develop neoplastic lesions in immunocompromised settings only. These results suggest that tetraploidy is particularly oncogenic in the context of deficient immunosurveillance.

Original languageEnglish
Pages (from-to)473-479
Number of pages7
JournalCell Cycle
Volume12
Issue number3
DOIs
Publication statusPublished - Feb 1 2013

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Immunologic Monitoring
Tetraploidy
Organoids
Colon
Carcinogenesis
Calreticulin
Subcutaneous Injections
Diploidy
Cell Size
Colonic Neoplasms
Neoplasms
Pharmaceutical Preparations
Proteins
In Vitro Techniques

Keywords

  • Apoptosis
  • Cell cycle
  • Cytochalasin D
  • Mitotic catastrophe
  • Nocodazole
  • P53

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Boilève, A., Senovilla, L., Vitale, I., Lissa, D., Martins, I., Métivier, D., ... Kroemer, G. (2013). Immunosurveillance against tetraploidization-induced colon tumorigenesis. Cell Cycle, 12(3), 473-479. https://doi.org/10.4161/cc.23369

Immunosurveillance against tetraploidization-induced colon tumorigenesis. / Boilève, Alice; Senovilla, Laura; Vitale, Ilio; Lissa, Delphine; Martins, Isabelle; Métivier, Didier; Van Den Brink, Stieneke; Clevers, Hans; Galluzzi, Lorenzo; Castedo, Maria; Kroemer, Guido.

In: Cell Cycle, Vol. 12, No. 3, 01.02.2013, p. 473-479.

Research output: Contribution to journalArticle

Boilève, A, Senovilla, L, Vitale, I, Lissa, D, Martins, I, Métivier, D, Van Den Brink, S, Clevers, H, Galluzzi, L, Castedo, M & Kroemer, G 2013, 'Immunosurveillance against tetraploidization-induced colon tumorigenesis', Cell Cycle, vol. 12, no. 3, pp. 473-479. https://doi.org/10.4161/cc.23369
Boilève A, Senovilla L, Vitale I, Lissa D, Martins I, Métivier D et al. Immunosurveillance against tetraploidization-induced colon tumorigenesis. Cell Cycle. 2013 Feb 1;12(3):473-479. https://doi.org/10.4161/cc.23369
Boilève, Alice ; Senovilla, Laura ; Vitale, Ilio ; Lissa, Delphine ; Martins, Isabelle ; Métivier, Didier ; Van Den Brink, Stieneke ; Clevers, Hans ; Galluzzi, Lorenzo ; Castedo, Maria ; Kroemer, Guido. / Immunosurveillance against tetraploidization-induced colon tumorigenesis. In: Cell Cycle. 2013 ; Vol. 12, No. 3. pp. 473-479.
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