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.

Senovilla, L., Vitale, I., Martins, I., Tailler, M., Pailleret, C., Michaud, M., et al. (2012). An immunosurveillance mechanism controls cancer cell ploidy. SCIENCE, 337(6102), 1678-1684 [10.1126/science.1224922].

An immunosurveillance mechanism controls cancer cell ploidy

VITALE , ILIO;PIACENTINI, MAURO;
2012-09-28

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.
28-set-2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Immunologic Surveillance; Animals; Humans; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Cell Line, Tumor; Mice; Mice, Inbred BALB C; DNA, Neoplasm; Neoplasms; Phosphorylation; Immunocompetence; Ploidies; Calreticulin; Common Variable Immunodeficiency
Senovilla, L., Vitale, I., Martins, I., Tailler, M., Pailleret, C., Michaud, M., et al. (2012). An immunosurveillance mechanism controls cancer cell ploidy. SCIENCE, 337(6102), 1678-1684 [10.1126/science.1224922].
Senovilla, L; Vitale, I; Martins, I; Tailler, M; Pailleret, C; Michaud, M; Galluzzi, L; Adjemian, S; Kepp, O; Niso Santano, M; Shen, S; Mariño, G; Criollo, A; Boilève, A; Job, B; Ladoire, S; Ghiringhelli, F; Sistigu, A; Yamazaki, T; Rello Varona, S; Locher, C; Poirier Colame, V; Talbot, M; Valent, A; Berardinelli, F; Antoccia, A; Ciccosanti, F; Fimia, G; Piacentini, M; Fueyo, A; Messina, N; Li, M; Chan, C; Sigl, V; Pourcher, G; Ruckenstuhl, C; Carmona Gutierrez, D; Lazar, V; Penninger, J; Madeo, F; López Otín, C; Smyth, M; Zitvogel, L; Castedo, M; Kroemer, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/78054
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