The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis.

Abstract:

:Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells. We provide evidence that Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells, to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells are selectively endowed with Dectin-2-dependent phagocytotic activity, with neither bone marrow-derived macrophages nor alveolar macrophages showing this potential. Concordantly, subcutaneous primary tumor growth and lung metastasis are not affected by the absence of Dectin-2. In addition, macrophage C-type lectin, a CLR known to be complex with Dectin-2, also contributes to the suppression of liver metastasis. Collectively, these results highlight the hitherto poorly understood mechanism of Kupffer cell-mediated control of metastasis that is mediated by the CLR innate receptor family, with implications for the development of anticancer therapy targeting CLRs.

authors

Kimura Y,Inoue A,Hangai S,Saijo S,Negishi H,Nishio J,Yamasaki S,Iwakura Y,Yanai H,Taniguchi T

doi

10.1073/pnas.1617903113

subject

Has Abstract

pub_date

2016-12-06 00:00:00

pages

14097-14102

issue

49

eissn

0027-8424

issn

1091-6490

pii

1617903113

journal_volume

113

pub_type

杂志文章
  • Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.

    abstract::Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identif...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.6.2355

    authors: Doudna JA,Cech TR,Sullenger BA

    更新日期:1995-03-14 00:00:00

  • Relationships between cortical myeloarchitecture and electrophysiological networks.

    abstract::The human brain relies upon the dynamic formation and dissolution of a hierarchy of functional networks to support ongoing cognition. However, how functional connectivities underlying such networks are supported by cortical microstructure remains poorly understood. Recent animal work has demonstrated that electrical a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1608587113

    authors: Hunt BA,Tewarie PK,Mougin OE,Geades N,Jones DK,Singh KD,Morris PG,Gowland PA,Brookes MJ

    更新日期:2016-11-22 00:00:00

  • Chromatin configuration of the human CD2 gene locus during T-cell development.

    abstract::To investigate the molecular basis for the tissue-specific expression of the human CD2 gene, its chromatin configuration was assessed by determining DNase I hypersensitivity and the degree of methylation during T-cell lineage commitment and development. Tissue-specific DNase I-hypersensitive sites were found within th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.11.4195

    authors: Wotton D,Flanagan BF,Owen MJ

    更新日期:1989-06-01 00:00:00

  • Primary structure of Escherichia coli ribosomal protein S1 and of its gene rpsA.

    abstract::The primary structure of proteins S1, the largest protein component of the Escherichia coli ribosome, has been elucidated by determining the amino acid sequence of the protein (from E. coli MRE600) and the nucleotide sequence of the S1 gene (rpsA, of a K-12 strain). The two methods gave results in perfect agreement ex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.4.1008

    authors: Schnier J,Kimura M,Foulaki K,Subramanian AR,Isono K,Wittmann-Liebold B

    更新日期:1982-02-01 00:00:00

  • Gene repression by the ferric uptake regulator in Pseudomonas aeruginosa: cycle selection of iron-regulated genes.

    abstract::The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). Novel targets of the Fur protein were isolated in a powerful SELEX (systematic evolution of ligands by exponential enrichment)-like cycle selection consisting of in vitro DNA-Fur ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.9.4409

    authors: Ochsner UA,Vasil ML

    更新日期:1996-04-30 00:00:00

  • Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBx).

    abstract::A stable free-radical polymeric derivative of prostaglandin B1 (PGBx) has been synthesized that exhibits regenerative effects on oxidative phosphorylation in aged mitochondria. The molecular weights of the most active preparations fall between 2000 and 2600. PGBx is characterized by a single-line electron spin resonan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.4.1598

    authors: Polis BD,Polis E,Kwong S

    更新日期:1979-04-01 00:00:00

  • A theory of distortion of the reaction zone.

    abstract::A cylindrical detonating explosive behaves like a non-Newtonian viscous fluid emerging from a cylindrical pipe. The expression for non-Newtonian viscous flow has been applied to detonating explosives. The resultant fit to emerging flame fronts from detonation is excellent for a wide variety of detonating explosives bo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.10.5575

    authors: Coon N,Ma SM,Redington PK,Brown B,Eyring H

    更新日期:1980-10-01 00:00:00

  • Establishing genetic transformation for comparative developmental studies in the crustacean Parhyale hawaiensis.

    abstract::The amphipod crustacean Parhyale hawaiensis has been put forward as an attractive organism for evolutionary developmental comparisons, and considerable effort is being invested in isolating developmental genes and studying their expression patterns in this species. The scope of these studies could be significantly exp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0501101102

    authors: Pavlopoulos A,Averof M

    更新日期:2005-05-31 00:00:00

  • Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes.

    abstract::The anticancer peptide PNC-27, which contains an HDM-2-binding domain corresponding to residues 12-26 of p53 and a transmembrane-penetrating domain, has been found to kill cancer cells (but not normal cells) by inducing membranolysis. We find that our previously determined 3D structure of the p53 residues of PNC-27 is...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0909364107

    authors: Sarafraz-Yazdi E,Bowne WB,Adler V,Sookraj KA,Wu V,Shteyler V,Patel H,Oxbury W,Brandt-Rauf P,Zenilman ME,Michl J,Pincus MR

    更新日期:2010-02-02 00:00:00

  • Neuroanatomical correlates of encoding in episodic memory: levels of processing effect.

    abstract::Cognitive studies of memory processes demonstrate that memory for stimuli is a function of how they are encoded; stimuli processed semantically are better remembered than those processed in a perceptual or shallow fashion. This study investigates the neural correlates of this cognitive phenomenon. Twelve subjects perf...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.6.2008

    authors: Kapur S,Craik FI,Tulving E,Wilson AA,Houle S,Brown GM

    更新日期:1994-03-15 00:00:00

  • Biologically templated organic polymers with nanoscale order.

    abstract::Methods for the construction of ordered nanoscale arrays have been implicated in fields ranging from separation technologies to microelectronics. Yet, despite the plethora of nanoscale structures assembled in nature that use a templating strategy, chemists have been unable to replicate this success. A technology is re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711308105

    authors: Willis B,Eubanks LM,Wood MR,Janda KD,Dickerson TJ,Lerner RA

    更新日期:2008-02-05 00:00:00

  • Myofibrillogenesis visualized in living embryonic cardiomyocytes.

    abstract::Myofibril formation was visualized in cultured live cardiomyocytes that were transfected with plasmids expressing green fluorescent protein (GFP) linked to the Z-band protein, alpha-actinin. The expression of this fluorescent protein provided an in vivo label for structures containing alpha-actinin. The GFP-alpha-acti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.17.9493

    authors: Dabiri GA,Turnacioglu KK,Sanger JM,Sanger JW

    更新日期:1997-08-19 00:00:00

  • Hydroxyl radical "footprinting" of RNA: application to pre-mRNA splicing complexes.

    abstract::We present an adaptation of the hydroxyl radical DNA "footprinting" technique that permits high-resolution mapping of protected regions of RNA. Hydroxyl radical cleaves RNA independently of base sequence and secondary structure of the RNAs examined and allows resolution of protected regions at the single nucleotide le...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.20.7795

    authors: Wang XD,Padgett RA

    更新日期:1989-10-01 00:00:00

  • CD1d-Restricted pathways in hepatocytes control local natural killer T cell homeostasis and hepatic inflammation.

    abstract::Invariant natural killer T (iNKT) cells recognize lipid antigens presented by CD1d and play a central role in regulating immunity and inflammation in peripheral tissues. However, the mechanisms which govern iNKT cell homeostasis after thymic emigration are incompletely understood. Here we demonstrate that microsomal t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1701428114

    authors: Zeissig S,Peuker K,Iyer S,Gensollen T,Dougan SK,Olszak T,Kaser A,Blumberg RS

    更新日期:2017-09-26 00:00:00

  • Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.

    abstract::Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically cyclized, yielding molecules with defined cyclization patterns that are crucial for polyketide bioactivity. The aromatase/cyclases (ARO/CYCs) are respon...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1512976112

    authors: Caldara-Festin G,Jackson DR,Barajas JF,Valentic TR,Patel AB,Aguilar S,Nguyen M,Vo M,Khanna A,Sasaki E,Liu HW,Tsai SC

    更新日期:2015-12-15 00:00:00

  • Transducin translocation contributes to rod survival and enhances synaptic transmission from rods to rod bipolar cells.

    abstract::In rod photoreceptors, several phototransduction components display light-dependent translocation between cellular compartments. Notably, the G protein transducin translocates from rod outer segments to inner segments/spherules in bright light, but the functional consequences of translocation remain unclear. We genera...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1222666110

    authors: Majumder A,Pahlberg J,Boyd KK,Kerov V,Kolandaivelu S,Ramamurthy V,Sampath AP,Artemyev NO

    更新日期:2013-07-23 00:00:00

  • Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d.

    abstract::Natural killer T (NKT) cells provide an innate-type immune response upon T cell receptor interaction with CD1d-presented antigens. We demonstrate through equilibrium tetramer binding and antigen presentation assays with Valpha14i-positive NKT cell hybridomas that the Sphingomonas glycolipid alpha-galacturonosyl cerami...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0600285103

    authors: Wu D,Zajonc DM,Fujio M,Sullivan BA,Kinjo Y,Kronenberg M,Wilson IA,Wong CH

    更新日期:2006-03-14 00:00:00

  • The diploid genome sequence of Candida albicans.

    abstract::We present the diploid genome sequence of the fungal pathogen Candida albicans. Because C. albicans has no known haploid or homozygous form, sequencing was performed as a whole-genome shotgun of the heterozygous diploid genome in strain SC5314, a clinical isolate that is the parent of strains widely used for molecular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0401648101

    authors: Jones T,Federspiel NA,Chibana H,Dungan J,Kalman S,Magee BB,Newport G,Thorstenson YR,Agabian N,Magee PT,Davis RW,Scherer S

    更新日期:2004-05-11 00:00:00

  • In vivo response of murine gamma delta T cells to a heat shock protein-derived peptide.

    abstract::Recent results suggested that a large subset of heat shock protein HSP-60 reactive peripheral lymphoid gamma delta T cells preexists in normal adult mice, all members of which respond to a single segment of this common HSP. However, the experimental evidence supporting this idea involved in vitro peptide responses of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.1.322

    authors: Fu YX,Cranfill R,Vollmer M,Van Der Zee R,O'Brien RL,Born W

    更新日期:1993-01-01 00:00:00

  • The pituitary gland is required for protection against lethal effects of Salmonella typhimurium.

    abstract::One-half of pituitary-intact or sham-operated rats survive infection with 10(9) colony-forming units of Salmonella typhimurium, whereas rats without a pituitary gland all die within a few days. When the dose of S. typhimurium is reduced 600-fold, 15-25% of the hypophysectomized rats survive, and the survival rate is s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.6.2274

    authors: Edwards CK 3rd,Yunger LM,Lorence RM,Dantzer R,Kelley KW

    更新日期:1991-03-15 00:00:00

  • Phorbol 12-myristate 13-acetate and insulin increase the concentration of fructose 2,6-bisphosphate and stimulate glycolysis in chicken embryo fibroblasts.

    abstract::Incubation of chicken embryo fibroblasts with mitogenic concentrations of insulin for 24 hr or with the tumor promoter phorbol 12-myristate 13-acetate for 6 hr stimulated lactate release and 3-O-methylglucose uptake. Insulin also increased the Vmax of 6-phosphofructo-1-kinase (ATP:D-fructose-6-phosphate 1-phosphotrans...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.19.6440

    authors: Bosca L,Rousseau GG,Hue L

    更新日期:1985-10-01 00:00:00

  • Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons.

    abstract::We have recently shown that the expression of nestin, the neural stem cell marker protein, is expressed in bulge-area stem cells of the hair follicle. We used transgenic mice with GFP expression driven by the nestin regulatory element [nestin-driven GFP (ND-GFP)]. The ND-GFP stem cells give rise to the outer-root shea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0501263102

    authors: Amoh Y,Li L,Katsuoka K,Penman S,Hoffman RM

    更新日期:2005-04-12 00:00:00

  • Cholesterol depletion induces large scale domain segregation in living cell membranes.

    abstract::Local inhomogeneities in lipid composition play a crucial role in regulation of signal transduction and membrane traffic. Nevertheless, most evidence for microdomains in cells remains indirect, and the nature of membrane inhomogeneities has been difficult to characterize. We used lipid analogs and lipid-anchored prote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.231377398

    authors: Hao M,Mukherjee S,Maxfield FR

    更新日期:2001-11-06 00:00:00

  • Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target.

    abstract::Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that gliob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0608396103

    authors: Horvath S,Zhang B,Carlson M,Lu KV,Zhu S,Felciano RM,Laurance MF,Zhao W,Qi S,Chen Z,Lee Y,Scheck AC,Liau LM,Wu H,Geschwind DH,Febbo PG,Kornblum HI,Cloughesy TF,Nelson SF,Mischel PS

    更新日期:2006-11-14 00:00:00

  • Synthetic LXR ligand inhibits the development of atherosclerosis in mice.

    abstract::The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux in macrophages, promotes bile acid synthesis in liver, and inhibits intestinal cholesterol absorption, actions that...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.112059299

    authors: Joseph SB,McKilligin E,Pei L,Watson MA,Collins AR,Laffitte BA,Chen M,Noh G,Goodman J,Hagger GN,Tran J,Tippin TK,Wang X,Lusis AJ,Hsueh WA,Law RE,Collins JL,Willson TM,Tontonoz P

    更新日期:2002-05-28 00:00:00

  • Poly(L-alanine) as a universal reference material for understanding protein energies and structures.

    abstract::We present a proposition, the "poly(L-alanine) hypothesis," which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L-alanine) of the same number of residues. Using a molecular mechanics force field to represent the releva...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.23.11513

    authors: Head-Gordon T,Stillinger FH,Wright MH,Gay DM

    更新日期:1992-12-01 00:00:00

  • Self-enforcing strategies to deter free-riding in the climate change mitigation game and other repeated public good games.

    abstract::As the Copenhagen Accord indicates, most of the international community agrees that global mean temperature should not be allowed to rise more than two degrees Celsius above preindustrial levels to avoid unacceptable damages from climate change. The scientific evidence distilled in the Fourth Assessment Report of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1106265108

    authors: Heitzig J,Lessmann K,Zou Y

    更新日期:2011-09-20 00:00:00

  • Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.

    abstract::Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are currently in clinical development in melanoma, a tumor that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1901323116

    authors: AbuHammad S,Cullinane C,Martin C,Bacolas Z,Ward T,Chen H,Slater A,Ardley K,Kirby L,Chan KT,Brajanovski N,Smith LK,Rao AD,Lelliott EJ,Kleinschmidt M,Vergara IA,Papenfuss AT,Lau P,Ghosh P,Haupt S,Haupt Y,Sanij E,

    更新日期:2019-09-03 00:00:00

  • Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

    abstract::Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunoc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314483110

    authors: Grigg P,Titong A,Jones LA,Yilma TD,Verardi PH

    更新日期:2013-09-17 00:00:00

  • Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

    abstract::The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2018078118

    authors: Hyun M,Taranda J,Radeljic G,Miner L,Wang W,Ochandarena N,Huang KW,Osten P,Sabatini BL

    更新日期:2021-01-05 00:00:00