An Immunosurveillance Mechanism Controls Cancer Cell Ploidy

被引：365

作者：

Senovilla, Laura ^{[1
,2
,3
]}

Vitale, Ilio ^{[1
,2
,3
]}

Martins, Isabelle ^{[1
,2
,3
]}

Tailler, Maximilien ^{[1
,2
,3
]}

Pailleret, Claire ^{[1
,2
,3
]}

Michaud, Mickael ^{[1
,2
,3
]}

Galluzzi, Lorenzo ^{[1
,2
,3
]}

Adjemian, Sandy ^{[1
,2
,3
]}

Kepp, Oliver ^{[1
,2
,3
]}

Niso-Santano, Mireia ^{[1
,2
,3
]}

Shen, Shensi ^{[1
,2
,3
]}

Marino, Guillermo ^{[1
,2
,3
]}

Criollo, Alfredo ^{[1
,2
,3
]}

Boileve, Alice ^{[1
,2
,3
]}

Job, Bastien ^{[1
,4
,5
]}

Ladoire, Sylvain ^{[6
,7
]}

Ghiringhelli, Francois ^{[6
,7
]}

Sistigu, Antonella ^{[1
,3
,8
]}

Yamazaki, Takahiro ^{[1
,3
,8
]}

Rello-Varona, Santiago ^{[1
,2
,3
]}

Locher, Clara ^{[1
,3
,8
]}

Poirier-Colame, Vichnou ^{[1
,3
,8
]}

Talbot, Monique ^{[1
]}

Valent, Alexander ^{[9
]}

Berardinelli, Francesco ^{[10
]}

Antoccia, Antonio ^{[10
]}

Ciccosanti, Fabiola ^{[11
]}

Fimia, Gian Maria ^{[11
]}

Piacentini, Mauro ^{[11
,12
]}

Fueyo, Antonio ^{[13
]}

Messina, Nicole L. ^{[14
,15
]}

Li, Ming ^{[14
]}

Chan, Christopher J. ^{[14
,16
]}

Sigl, Verena ^{[17
]}

Pourcher, Guillaume ^{[3
,18
,19
]}

Ruckenstuhl, Christoph ^{[20
]}

Carmona-Gutierrez, Didac ^{[20
]}

Lazar, Vladimir ^{[1
,4
,5
]}

Penninger, Josef M. ^{[17
]}

Madeo, Frank ^{[20
]}

Lopez-Otin, Carlos ^{[21
]}

Smyth, Mark J. ^{[14
]}

Zitvogel, Laurence ^{[1
,3
,8
,22
]}

Castedo, Maria ^{[1
,2
,3
]}

Kroemer, Guido ^{[1
,2
,23
,24
,25
]}

机构：

[1] Inst Gustave Roussy, Villejuif, France

[2] INSERM, U848, Villejuif, France

[3] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France

[4] Unite Genom Fonct & Bioinformat, Villejuif, France

[5] Genom Platform, Villejuif, France

[6] Georges Francois Leclerc Ctr, Dept Med Oncol, Dijon, France

[7] Univ Burgundy, CRI 866, Avenir Team, INSERM, Dijon, France

[8] INSERM, U1015, Villejuif, France

[9] Dept Biol & Pathol Med, Villejuif, France

[10] Univ Roma Tre, Dipartimento Biol, Rome, Italy

[11] Natl Inst Infect Dis L Spallanzani, Rome, Italy

[12] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy

[13] Univ Oviedo, Inst Univ Oncol IUOPA, Fac Med, Dept Biol Func, Oviedo, Spain

[14] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic, Australia

[15] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia

[16] Monash Univ, Dept Immunol, Prahran, Vic, Australia

[17] Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna, Austria

[18] Antoine Beclere Hosp, AP HP, Dept Minimal Invas Surg, Clamart, France

[19] INSERM, U972, F-94275 Le Kremlin Bicetre, France

[20] Inst Mol Biosci, Graz, Austria

[21] Univ Oviedo, IUOPA, Fac Med, Dept Bioquim & Biol Mol, Oviedo, Spain

[22] Ctr Clin Invest Biotherapies Canc CICBT 507, Villejuif, France

[23] Ctr Rech Cordeliers, Paris, France

[24] Hop Europeen Georges Pompidou, AP HP, Paris, France

[25] Univ Paris 05, Paris, France

来源：

SCIENCE | 2012年 / 337卷 / 6102期

基金：

欧洲研究理事会; 英国医学研究理事会; 奥地利科学基金会;

关键词：

CALRETICULIN EXPOSURE; ADAPTIVE IMMUNITY; IMMUNOGENICITY; TETRAPLOIDY; CLEARANCE; MITOSIS; DEATH; P53;

D O I：

10.1126/science.1224922

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：1678 / 1684

页数：8

共 34 条

[1]

The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe [J].