Document Detail

An immunosurveillance mechanism controls cancer cell ploidy.
MedLine Citation:
PMID:  23019653     Owner:  NLM     Status:  MEDLINE    
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.
Laura Senovilla; Ilio Vitale; Isabelle Martins; Maximilien Tailler; Claire Pailleret; Mickaël Michaud; Lorenzo Galluzzi; Sandy Adjemian; Oliver Kepp; Mireia Niso-Santano; Shensi Shen; Guillermo Mariño; Alfredo Criollo; Alice Boilève; Bastien Job; Sylvain Ladoire; François Ghiringhelli; Antonella Sistigu; Takahiro Yamazaki; Santiago Rello-Varona; Clara Locher; Vichnou Poirier-Colame; Monique Talbot; Alexander Valent; Francesco Berardinelli; Antonio Antoccia; Fabiola Ciccosanti; Gian Maria Fimia; Mauro Piacentini; Antonio Fueyo; Nicole L Messina; Ming Li; Christopher J Chan; Verena Sigl; Guillaume Pourcher; Christoph Ruckenstuhl; Didac Carmona-Gutierrez; Vladimir Lazar; Josef M Penninger; Frank Madeo; Carlos López-Otín; Mark J Smyth; Laurence Zitvogel; Maria Castedo; Guido Kroemer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  337     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-28     Completed Date:  2012-10-02     Revised Date:  2012-12-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1678-84     Citation Subset:  IM    
INSERM, U848, Villejuif, France.
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MeSH Terms
Calreticulin / immunology
Cell Line, Tumor
Common Variable Immunodeficiency / genetics
DNA, Neoplasm / analysis,  genetics
Endoplasmic Reticulum Stress / immunology*
Eukaryotic Initiation Factor-2 / metabolism
Immunologic Surveillance*
Mice, Inbred BALB C
Neoplasms / chemically induced,  genetics*,  immunology*
Reg. No./Substance:
0/Calreticulin; 0/DNA, Neoplasm; 0/Eukaryotic Initiation Factor-2
Comment In:
Science. 2012 Sep 28;337(6102):1616-7   [PMID:  23019639 ]
Nat Rev Immunol. 2012 Nov;12(11):745   [PMID:  23037554 ]

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