G. P. Dunn, L. J. Old, and R. D. Schreiber, The Immunobiology of Cancer Immunosurveillance and Immunoediting, Immunity, vol.21, issue.2, pp.137-148, 2004.
DOI : 10.1016/j.immuni.2004.07.017

A. Hilliard, B. Hilliard, S. J. Zheng, H. Sun, T. Miwa et al., Translational Regulation of Autoimmune Inflammation and Lymphoma Genesis by Programmed Cell Death 4, The Journal of Immunology, vol.177, issue.11, pp.8095-8102, 2006.
DOI : 10.4049/jimmunol.177.11.8095

M. Yasuda, T. Schmid, D. Rübsamen, N. H. Colburn, K. Irie et al., Downregulation of programmed cell death 4 by inflammatory conditions contributes to the generation of the tumor promoting microenvironment, Molecular Carcinogenesis, vol.170, pp.837-848, 2010.
DOI : 10.1002/mc.20660

F. J. Sheedy, E. Palsson-mcdermott, E. J. Hennessy, C. Martin, J. J. O-'leary et al., Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21, Nature Immunology, vol.175, issue.2, pp.141-147, 2010.
DOI : 10.1073/pnas.160027697

B. Lankat-buttgereit and R. Göke, The tumour suppressor Pdcd4: recent advances in the elucidation of function and regulation, Biology of the Cell, vol.18, issue.6, pp.309-317, 2009.
DOI : 10.1042/BC20080191

P. P. Reis, M. Tomenson, N. K. Cervigne, J. Machado, I. Jurisica et al., Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma, Molecular Cancer, vol.9, issue.1, p.238, 2010.
DOI : 10.1186/1476-4598-9-238

Y. K. Kim, J. T. Kwon, J. Y. Choi, H. L. Jiang, R. Arote et al., Suppression of tumor growth in xenograft model mice by programmed cell death 4 gene delivery using folate-PEG-baculovirus, Cancer Gene Therapy, vol.59, issue.11, pp.751-760, 2010.
DOI : 10.1016/S0161-5890(02)00252-3

H. S. Yang, A. P. Jansen, A. A. Komar, X. Zheng, W. C. Merrick et al., The Transformation Suppressor Pdcd4 Is a Novel Eukaryotic Translation Initiation Factor 4A Binding Protein That Inhibits Translation, Molecular and Cellular Biology, vol.23, issue.1, pp.26-37, 2003.
DOI : 10.1128/MCB.23.1.26-37.2003

N. V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N. H. Colburn, N. E. Sherman et al., S6K1- and ??TRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth, Science, vol.314, issue.5798, pp.467-471, 2006.
DOI : 10.1126/science.1130276

I. A. Asangani, S. A. Rasheed, D. A. Nikolova, J. H. Leupold, N. H. Colburn et al., MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer, Oncogene, vol.62, issue.15, pp.2128-2136, 2008.
DOI : 10.1074/jbc.M611393200

H. Allgayer, Pdcd4, a colon cancer prognostic that is regulated by a microRNA, Critical Reviews in Oncology/Hematology, vol.73, issue.3, pp.185-191, 2010.
DOI : 10.1016/j.critrevonc.2009.09.001

W. Roa, B. Brunet, L. Guo, J. Amanie, A. Fairchild et al., Identification of a new microRNA expression profile as a potential cancer screening tool, Clin. Invest. Med, vol.33, p.124, 2010.

M. E. Hatley, D. M. Patrick, M. R. Garcia, J. A. Richardson, R. Bassel-duby et al., Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21, Cancer Cell, vol.18, issue.3, pp.282-293, 2010.
DOI : 10.1016/j.ccr.2010.08.013

B. N. Davis, A. C. Hilyard, G. Lagna, and A. Hata, SMAD proteins control DROSHA-mediated microRNA maturation, Nature, vol.94, issue.7200, pp.56-61, 2008.
DOI : 10.1038/nature07086

Q. Yao, S. Cao, C. Li, A. Mengesha, B. Kong et al., Micro-RNA-21 regulates TGF-??-induced myofibroblast differentiation by targeting PDCD4 in tumor-stroma interaction, International Journal of Cancer, vol.272, issue.8, pp.1783-1792, 2011.
DOI : 10.1002/ijc.25506

S. Goldoni, D. G. Seidler, J. Heath, M. Fassan, R. Baffa et al., An Antimetastatic Role for Decorin in Breast Cancer, The American Journal of Pathology, vol.173, issue.3, pp.844-855, 2008.
DOI : 10.2353/ajpath.2008.080275

L. Sorokin, The impact of the extracellular matrix on inflammation, Nature Reviews Immunology, vol.114, issue.10, pp.712-723, 2010.
DOI : 10.1038/nri2852

L. Schaefer, Extracellular matrix molecules: endogenous danger signals as new drug targets in kidney diseases, Current Opinion in Pharmacology, vol.10, issue.2, pp.185-190, 2010.
DOI : 10.1016/j.coph.2009.11.007

G. Y. Chen and G. Nuñez, Sterile inflammation: sensing and reacting to damage, Nature Reviews Immunology, vol.464, issue.12, pp.826-837, 2010.
DOI : 10.1038/nri2873

R. V. Iozzo and L. Schaefer, Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans, FEBS Journal, vol.274, issue.Suppl. 4, pp.3864-3875, 2010.
DOI : 10.1111/j.1742-4658.2010.07797.x

W. A. Border, N. A. Noble, T. Yamamoto, J. R. Harper, Y. Yamaguchi et al., Natural inhibitor of transforming growth factor-?? protects against scarring in experimental kidney disease, Nature, vol.360, issue.6402, pp.361-364, 1992.
DOI : 10.1038/360361a0

Y. Yamaguchi, D. M. Mann, and E. Ruoslahti, Negative regulation of transforming growth factor-?? by the proteoglycan decorin, Nature, vol.346, issue.6281, pp.281-284, 1990.
DOI : 10.1038/346281a0

S. Goldoni and R. V. Iozzo, Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs, International Journal of Cancer, vol.16, issue.11, pp.2473-2479, 2008.
DOI : 10.1002/ijc.23930

J. Köninger, N. A. Giese, M. Bartel, F. F. Di-mola, P. O. Berberat et al., The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis, Journal of Clinical Pathology, vol.59, issue.1, pp.21-27, 2006.
DOI : 10.1136/jcp.2004.023135

J. Xaus, M. Comalada, M. Cardó, A. F. Valledor, and A. Celada, Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27Kip1 and p21Waf1, Blood, vol.98, issue.7, pp.2124-2133, 2001.
DOI : 10.1182/blood.V98.7.2124

M. Comalada, M. Cardó, J. Xaus, A. F. Valledor, J. Lloberas et al., Decorin Reverses the Repressive Effect of Autocrine-Produced TGF-?? on Mouse Macrophage Activation, The Journal of Immunology, vol.170, issue.9, pp.4450-4456, 2003.
DOI : 10.4049/jimmunol.170.9.4450

D. J. Berg, R. Kühn, K. Rajewsky, W. Müller, S. Menon et al., Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance., Journal of Clinical Investigation, vol.96, issue.5, pp.2339-2347, 1995.
DOI : 10.1172/JCI118290

L. Schaefer, A. Babelova, E. Kiss, H. J. Hausser, M. Baliova et al., The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages, Journal of Clinical Investigation, vol.115, issue.8, pp.2223-2233, 2005.
DOI : 10.1172/JCI23755DS1

R. Shimazu, S. Akashi, H. Ogata, Y. Nagai, K. Fukudome et al., MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4, The Journal of Experimental Medicine, vol.161, issue.11, pp.1777-1782, 1999.
DOI : 10.1084/jem.180.4.1217

T. Kawai and S. Akira, The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors, Nature Immunology, vol.1799, issue.5, pp.373-384, 2010.
DOI : 10.1126/science.1179050

J. G. Tralhão, L. Schaefer, M. Micegova, C. Evaristo, E. Schönherr et al., In vivo selective and distant killing of cancer cells, using adenovirus-mediated decorin gene transfer, The FASEB Journal, vol.17, pp.464-466, 2003.
DOI : 10.1096/fj.02-0534fje

D. G. Seidler, S. Goldoni, C. Agnew, C. Cardi, M. L. Thakur et al., Decorin Protein Core Inhibits in Vivo Cancer Growth and Metabolism by Hindering Epidermal Growth Factor Receptor Function and Triggering Apoptosis via Caspase-3 Activation, Journal of Biological Chemistry, vol.281, issue.36, pp.26408-26418, 2006.
DOI : 10.1074/jbc.M602853200

M. Strazynski, J. A. Eble, H. Kresse, and E. Schönherr, Interleukin (IL)-6 and IL-10 Induce Decorin mRNA in Endothelial Cells, but Interaction with Fibrillar Collagen Is Essential for Its Translation, Journal of Biological Chemistry, vol.279, issue.20, pp.21266-21270, 2004.
DOI : 10.1074/jbc.M309782200

A. Babelova, K. Moreth, W. Tsalastra-greul, J. Zeng-brouwers, O. Eickelberg et al., Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors, Journal of Biological Chemistry, vol.284, issue.36, pp.24035-24048, 2009.
DOI : 10.1074/jbc.M109.014266

K. Moreth, R. Brodbeck, A. Babelova, N. Gretz, T. Spieker et al., The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis, Journal of Clinical Investigation, vol.120, issue.12, pp.4251-4272, 2010.
DOI : 10.1172/JCI42213DS1

K. R. Taylor and R. L. Gallo, Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation, The FASEB Journal, vol.20, issue.1, pp.9-22, 2006.
DOI : 10.1096/fj.05-4682rev

R. C. Coll and L. A. , New Insights into the Regulation of Signalling by Toll-Like Receptors and Nod-Like Receptors, Journal of Innate Immunity, vol.2, issue.5, pp.406-421, 2010.
DOI : 10.1159/000315469

E. Schönherr, M. Broszat, E. Brandan, P. Bruckner, and H. Kresse, Decorin Core Protein Fragment Leu155-Val260 Interacts with TGF-?? but Does Not Compete for Decorin Binding to Type I Collagen, Archives of Biochemistry and Biophysics, vol.355, issue.2, pp.241-248, 1998.
DOI : 10.1006/abbi.1998.0720

R. Merline, R. M. Schaefer, and L. Schaefer, The matricellular functions of small leucine-rich proteoglycans (SLRPs), Journal of Cell Communication and Signaling, vol.284, issue.Pt 2, pp.323-335, 2009.
DOI : 10.1007/s12079-009-0066-2

M. A. Cassatella, L. Meda, S. Gasperini, F. Calzetti, and S. Bonora, Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation, Journal of Experimental Medicine, vol.179, issue.5
DOI : 10.1084/jem.179.5.1695

A. D. Andrea, M. Aste-amezaga, N. M. Valiante, X. Ma, M. Kubin et al., Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma- production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells, Journal of Experimental Medicine, vol.178, issue.3, pp.1041-1048, 1993.
DOI : 10.1084/jem.178.3.1041

L. B. Frankel, N. R. Christoffersen, A. Jacobsen, M. Lindow, A. Krogh et al., Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells, Journal of Biological Chemistry, vol.283, issue.2, pp.1026-1033, 2008.
DOI : 10.1074/jbc.M707224200

C. Cabello-verrugio and E. Brandan, A Novel Modulatory Mechanism of Transforming Growth Factor-beta Signaling through Decorin and LRP-1, Journal of Biological Chemistry, vol.282, issue.26, pp.18842-18850, 2007.
DOI : 10.1074/jbc.M700243200

K. M. Min and P. H. Kim, Macrophage-derived TGF-b1 induces IgA isotype expression, Mol. Cells, vol.16, pp.245-250, 2003.

E. Seki, S. De-minicis, C. H. Osterreicher, J. Kluwe, Y. Osawa et al., TLR4 enhances TGF-?? signaling and hepatic fibrosis, Nature Medicine, vol.41, issue.11, pp.1324-1332, 2007.
DOI : 10.1038/nm1663

M. Ständer, U. Naumann, W. Wick, and M. Weller, Transforming growth factor-?? and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth, Cell and Tissue Research, vol.296, issue.2, pp.221-227, 1999.
DOI : 10.1007/s004410051283

Y. Iwashita, T. Ogawa, S. Goto, M. Nakanishi, T. Goto et al., Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid], Cancer Gene Therapy, vol.11, issue.2, pp.103-108, 2004.
DOI : 10.1038/sj.cgt.7700669

M. Eisenring, J. Vom-berg, G. Kristiansen, E. Saller, and B. Becher, IL-12 initiates tumor rejection via lymphoid tissue???inducer cells bearing the natural cytotoxicity receptor NKp46, Nature Immunology, vol.174, issue.11, pp.1030-1038, 2010.
DOI : 10.1084/jem.20082492

A. G. Jarnicki, J. Lysaght, S. Todryk, and K. H. Mills, Suppression of Antitumor Immunity by IL-10 and TGF-??-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells, The Journal of Immunology, vol.177, issue.2, pp.896-904, 2006.
DOI : 10.4049/jimmunol.177.2.896

J. M. Yingling, K. L. Blanchard, and J. S. Sawyer, Development of TGF-?? signalling inhibitors for cancer therapy, Nature Reviews Drug Discovery, vol.9, issue.12, pp.1011-1022, 2004.
DOI : 10.1038/35094059

S. Troup, C. Njue, E. V. Kliewer, M. Parisien, C. Roskelley et al., Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer, Clin. Cancer Res, vol.9, pp.207-214, 2003.

A. Matsumine, K. Shintani, K. Kusuzaki, T. Matsubara, H. Satonaka et al., Expression of decorin, a small leucine-rich proteoglycan, as a prognostic factor in soft tissue tumors, Journal of Surgical Oncology, vol.70, issue.5, pp.411-418, 2007.
DOI : 10.1002/jso.20745

Y. Gu, S. Zhang, Q. Wu, S. Xu, Y. Cui et al., Differential expression of decorin, EGFR and cyclin D1 during mammary gland carcinogenesis in TA2 mice with spontaneous breast cancer, Journal of Experimental & Clinical Cancer Research, vol.29, issue.1, p.6, 2010.
DOI : 10.1186/1756-9966-29-6

N. Bitomsky, N. Wethkamp, R. Marikkannu, and K. H. Klempnauer, siRNA-mediated knockdown of Pdcd4 expression causes upregulation of p21(Waf1/Cip1) expression, Oncogene, vol.25, issue.35, pp.4820-4829, 2008.
DOI : 10.1038/onc.2008.115

R. V. Iozzo and R. D. Sanderson, Proteoglycans in cancer biology, tumour microenvironment and angiogenesis, Journal of Cellular and Molecular Medicine, vol.277, issue.5, pp.1013-1031, 2011.
DOI : 10.1111/j.1582-4934.2010.01236.x

A. D. Theocharis, S. S. Skandalis, G. N. Tzanakakis, and N. K. Karamanos, Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting, FEBS Journal, vol.281, issue.19, pp.3904-3923, 2010.
DOI : 10.1111/j.1742-4658.2010.07800.x

S. Goldoni, A. Humphries, A. Nystrom, S. Sattar, R. T. Owens et al., Decorin is a novel antagonistic ligand of the Met receptor, The Journal of Cell Biology, vol.19, issue.4, pp.743-754, 2009.
DOI : 10.1074/jbc.M503833200

Y. Hu, H. Sun, R. T. Owens, J. Wu, Y. Q. Chen et al., Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways, Neoplasia, vol.11, issue.10, pp.1042-1053, 2009.
DOI : 10.1593/neo.09760

S. Buraschi, N. Pal, N. Tyler-rubinstein, R. T. Owens, T. Neill et al., Decorin Antagonizes Met Receptor Activity and Down-regulates ??-Catenin and Myc Levels, Journal of Biological Chemistry, vol.285, issue.53, pp.42075-42085, 2010.
DOI : 10.1074/jbc.M110.172841

R. C. Bone, R. A. Balk, F. B. Cerra, R. P. Dellinger, A. M. Fein et al., Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis, The ACCP/SCCM Consensus Conference Committee, pp.1644-1655, 1992.
DOI : 10.1378/chest.101.6.1644

W. A. Knaus, E. A. Draper, D. P. Wagner, J. E. Zimmerman, and A. Ii, APACHE II, Critical Care Medicine, vol.13, issue.10, pp.818-829, 1985.
DOI : 10.1097/00003246-198510000-00009

L. Schaefer, W. Tsalastra, A. Babelova, M. Baliova, J. Minnerup et al., Decorin-Mediated Regulation of Fibrillin-1 in the Kidney Involves the Insulin-Like Growth Factor-I Receptor and Mammalian Target of Rapamycin, The American Journal of Pathology, vol.170, issue.1, pp.301-315, 2007.
DOI : 10.2353/ajpath.2007.060497

C. J. Wienken, P. Baaske, U. Rothbauer, D. Braun, and S. Duhr, Protein-binding assays in biological liquids using microscale thermophoresis, Nature Communications, vol.47, issue.7, p.100, 2010.
DOI : 10.1038/ncomms1093

(. R. Biomedicine, L. S. , N. , R. Ca39481, R. Ca47282 et al., Frankfurt International Research Graduate School for Translational Author contributions: R.M. did most of the in vivo and in vitro work. K.M. performed immunoprecipitations and binding assays and was involved in the transfection and in vivo experiments was involved in the in vivo experiments, qPCR, transfection , and immunostainings. M.V.N. was responsible for part of the Western blotting and binding assays was involved in the silencing experiments, performed adenoviral expression of decorin in tumors. R.M.S. was responsible for all of the human sepsis data. R.M.S. and J.P. co-designed the study. L.S. and R.V.I. conceived and designed the study. L.S., R.M.S., and R.V.I. wrote the manuscript. Competing interests: The authors declare that they have no competing financial interests, 1082.

R. Merline, K. Moreth, J. Beckmann, M. V. Nastase, J. Zeng-brouwers et al., Signaling by the Matrix Proteoglycan Decorin Controls Inflammation and Cancer Through PDCD4 and MicroRNA-21, Science Signaling, vol.4, issue.199, p.75, 2011.
DOI : 10.1126/scisignal.2001868

URL : https://hal.archives-ouvertes.fr/inserm-00642810