Comparative Proteomics Study Reveals That Bacterial CpG Motifs Induce Tumor Cell Autophagy in Vitro and in Vivo

被引:28
作者
Bertin, Samuel [2 ]
Samson, Michel [2 ,3 ]
Pons, Catherine [2 ]
Guigonis, Jean-Marie [2 ,3 ]
Gavelli, Adolfo [2 ,4 ]
Baque, Patrick [2 ,5 ]
Brossette, Nicole [2 ]
Pagnotta, Sophie [2 ,6 ]
Ricci, Jean-Ehrland [2 ,7 ]
Pierrefite-Carle, Valerie [1 ,2 ]
机构
[1] Fac Med, INSERM, U638, F-06107 Nice 2, France
[2] Univ Nice Sophia Antipolis, Fac Med, F-06107 Nice, France
[3] IFR50, F-06107 Nice, France
[4] Ctr Hosp Princesse Grace, Serv Chirurg Gen & Digest, MC-98000 Monaco, Monaco
[5] Hop St Roche, Serv Chirurg Urgence, F-06107 Nice, France
[6] Ctr Commun Microscopie Appl, F-06108 Nice, France
[7] INSERM, U895, Ctr Mediterraneen Med Mol C3M, Cell Death & Survival AVENIR Team, F-06204 Nice 3, France
关键词
D O I
10.1074/mcp.M800100-MCP200
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Unmethylated CpG dinucleotides, present in bacterial DNA, are recognized in vertebrates via the Toll-like receptor 9 (TLR9) and are known to act as an anticancer agent by stimulating immune cells to induce a proinflammatory response. Although the effects of CpG-oligodeoxynucleotides (CpG-ODNs) in immune cells have been widely studied, little is known regarding their molecular effects in TLR9-positive tumor cells. To better understand the role of these bacterial motifs in cancer cells, we analyzed proteome modifications induced in TLR9-positive tumor cells in vitro and in vivo after CpG-ODN treatment in a rat colon carcinoma model. Proteomics analysis of tumor cells by two-dimensional gel electrophoresis followed by mass spectrometry identified several proteins modulated by bacterial CpG motifs. Among them, several are related to autophagy including potential autophagic substrates. In addition, we observed an increased glyceraldehyde-3-phosphate dehydrogenase expression, which has been shown to be sufficient to trigger an autophagic process. Autophagy is a self-digestion pathway whereby cytoplasmic material is sequestered by a structure termed the autophagosome for subsequent degradation and recycling. As bacteria are known to trigger autophagy, we assessed whether bacterial CpG motifs might induce autophagy in TLR9-positive tumor cells. We showed that CpG-ODN can induce autophagy in rodent and human tumor cell lines and was TLR9-dependent. In addition, an increase in the number of autophagosomes can also be observed in vivo after CpG motif intratumoral injection. Our findings bring new insights on the effect of bacterial CpG motifs in tumor cells and may be relevant for cancer treatment and more generally for gene therapy approaches in TLR9-positive tissues. Molecular & Cellular Proteomics 7: 2311-2322, 2008.
引用
收藏
页码:2311 / 2322
页数:12
相关论文
共 46 条
[1]   Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NFκB-independent pathway [J].
Akhtar, M ;
Watson, JL ;
Nazli, A ;
McKay, DM .
FASEB JOURNAL, 2003, 17 (08) :1319-+
[2]   Innate immunity at the mucosal surface: Role of toll-like receptor 3 and toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens [J].
Andersen, JM ;
Al-Khairy, D ;
Ingalls, RR .
BIOLOGY OF REPRODUCTION, 2006, 74 (05) :824-831
[3]  
Bertin S, 2008, INT J MOL MED, V21, P309
[4]   Toll-like receptors mediate proliferation and survival of multiple myeloma cells [J].
Bohnhorst, J ;
Rasmussen, T ;
Moen, SH ;
Flottum, M ;
Knudsen, L ;
Borset, M ;
Espevik, T ;
Sundan, A .
LEUKEMIA, 2006, 20 (06) :1138-1144
[5]   Protein profiling of rat ventral prostate following chronic finasteride administration -: Identification and localization of a novel putative androgen-regulated protein [J].
Cayatte, Corinne ;
Pons, Catherine ;
Guigonis, Jean-Marie ;
Pizzol, Jerome ;
Elies, Laetitia ;
Kennel, Philippe ;
Rouquie, David ;
Bars, Remi ;
Rossi, Bernard ;
Samson, Michel .
MOLECULAR & CELLULAR PROTEOMICS, 2006, 5 (11) :2031-2043
[6]   INHIBITION OF PYRUVATE-CARBOXYLASE DEGRADATION AND TOTAL PROTEIN BREAKDOWN BY LYSOSOMOTROPIC AGENTS IN 3T3-L1 CELLS [J].
CHANDLER, CS ;
BALLARD, FJ .
BIOCHEMICAL JOURNAL, 1983, 210 (03) :845-853
[7]   GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation [J].
Colell, Anna ;
Ricci, Jean-Ehrland ;
Tait, Stephen ;
Milasta, Sandra ;
Maurer, Ulrich ;
Bouchier-Hayes, Lisa ;
Fitzgerald, Patrick ;
Guio-Carrion, Ana ;
Waterhouse, Nigel J. ;
Li, Cindy Wei ;
Mari, Bernard ;
Barbry, Pascal ;
Newmeyer, Donald D. ;
Beere, Helen M. ;
Green, Douglas R. .
CELL, 2007, 129 (05) :983-997
[8]   Selective degradation of annexins by chaperone-mediated autophagy [J].
Cuervo, AM ;
Gomes, AV ;
Barnes, JA ;
Dice, JF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (43) :33329-33335
[9]   A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins [J].
Cuervo, AM ;
Dice, JF ;
Knecht, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (09) :5606-5615
[10]   Does autophagy contribute to cell death? [J].
Debnath, Jayanta ;
Baehrecke, Eric H. ;
Kroemer, Guido .
AUTOPHAGY, 2005, 1 (02) :66-74