An immunosurveillance mechanism controls cancer cell ploidy. Academic Article uri icon

Overview

MeSH

  • Animals
  • Calreticulin
  • Cell Line, Tumor
  • Common Variable Immunodeficiency
  • DNA, Neoplasm
  • Eukaryotic Initiation Factor-2
  • Humans
  • Immunocompetence
  • Mice
  • Mice, Inbred BALB C
  • Phosphorylation

MeSH Major

  • Endoplasmic Reticulum Stress
  • Immunologic Surveillance
  • Neoplasms
  • Ploidies

abstract

  • Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers.

authors

publication date

  • September 28, 2012

has subject area

  • Animals
  • Calreticulin
  • Cell Line, Tumor
  • Common Variable Immunodeficiency
  • DNA, Neoplasm
  • Endoplasmic Reticulum Stress
  • Eukaryotic Initiation Factor-2
  • Humans
  • Immunocompetence
  • Immunologic Surveillance
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms
  • Phosphorylation
  • Ploidies

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1224922

PubMed ID

  • 23019653

Additional Document Info

start page

  • 1678

end page

  • 1684

volume

  • 337

number

  • 6102