Tumour exosome integrins determine organotropic metastasis.


:Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.






Hoshino A,Costa-Silva B,Shen TL,Rodrigues G,Hashimoto A,Tesic Mark M,Molina H,Kohsaka S,Di Giannatale A,Ceder S,Singh S,Williams C,Soplop N,Uryu K,Pharmer L,King T,Bojmar L,Davies AE,Ararso Y,Zhang T,Zhang H,Her




Has Abstract


2015-11-19 00:00:00
















  • Programmed population control by cell-cell communication and regulated killing.

    abstract::De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. Here we demonstrate that by coupling gene expression to cell survival and death using cell-cell communic...


    pub_type: 杂志文章


    authors: You L,Cox RS 3rd,Weiss R,Arnold FH

    更新日期:2004-04-22 00:00:00

  • Generation of an antibody with enhanced affinity and specificity for its antigen by protein engineering.

    abstract::A detailed description of the interactions between an antibody and its epitope is necessary to allow an understanding of the way in which antibodies bind to antigenic surfaces presented by foreign molecules. Ideally this should be done by analysis of crystal structures of antibody-antigen complexes, but so far only tw...


    pub_type: 杂志文章


    authors: Roberts S,Cheetham JC,Rees AR

    更新日期:1987-08-20 00:00:00

  • Macromolecular diffractive imaging using imperfect crystals.

    abstract::The three-dimensional structures of macromolecules and their complexes are mainly elucidated by X-ray protein crystallography. A major limitation of this method is access to high-quality crystals, which is necessary to ensure X-ray diffraction extends to sufficiently large scattering angles and hence yields informatio...


    pub_type: 杂志文章


    authors: Ayyer K,Yefanov OM,Oberthür D,Roy-Chowdhury S,Galli L,Mariani V,Basu S,Coe J,Conrad CE,Fromme R,Schaffer A,Dörner K,James D,Kupitz C,Metz M,Nelson G,Xavier PL,Beyerlein KR,Schmidt M,Sarrou I,Spence JC,Weierstall

    更新日期:2016-02-11 00:00:00

  • Diet-microbiota interactions as moderators of human metabolism.

    abstract::It is widely accepted that obesity and associated metabolic diseases, including type 2 diabetes, are intimately linked to diet. However, the gut microbiota has also become a focus for research at the intersection of diet and metabolic health. Mechanisms that link the gut microbiota with obesity are coming to light thr...


    pub_type: 杂志文章,评审


    authors: Sonnenburg JL,Bäckhed F

    更新日期:2016-07-07 00:00:00

  • Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.

    abstract::The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis an...


    pub_type: 杂志文章


    authors: Herndon LA,Schmeissner PJ,Dudaronek JM,Brown PA,Listner KM,Sakano Y,Paupard MC,Hall DH,Driscoll M

    更新日期:2002-10-24 00:00:00

  • Rights on DNA.

    abstract::A report adopted by the Council of Europe lists eight recommendations on the legal, ethical, and social issues raised by recombinant DNA research. The legislators stressed that the right to a "genetic inheritance free from any form of engineering" should be included in the European Human Rights Convention, and that s...


    pub_type: 新闻


    authors: Becker J

    更新日期:1982-02-18 00:00:00

  • Rare and low-frequency coding variants alter human adult height.

    abstract::Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per a...


    pub_type: 杂志文章


    authors: Marouli E,Graff M,Medina-Gomez C,Lo KS,Wood AR,Kjaer TR,Fine RS,Lu Y,Schurmann C,Highland HM,Rüeger S,Thorleifsson G,Justice AE,Lamparter D,Stirrups KE,Turcot V,Young KL,Winkler TW,Esko T,Karaderi T,Locke AE,Mas

    更新日期:2017-02-09 00:00:00

  • Pervasive roles of microRNAs in cardiovascular biology.

    abstract::First recognized as regulators of development in worms and fruitflies, microRNAs are emerging as pivotal modulators of mammalian cardiovascular development and disease. Individual microRNAs modulate the expression of collections of messenger RNA targets that often have related functions, thereby governing complex biol...


    pub_type: 杂志文章,评审


    authors: Small EM,Olson EN

    更新日期:2011-01-20 00:00:00

  • The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice.

    abstract::Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin mu or kappa enhancer frequently develop a fatal lymphoma within a few months of birth. Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at severa...


    pub_type: 杂志文章


    authors: Adams JM,Harris AW,Pinkert CA,Corcoran LM,Alexander WS,Cory S,Palmiter RD,Brinster RL

    更新日期:1985-12-12 00:00:00

  • Towards spike-based machine intelligence with neuromorphic computing.

    abstract::Guided by brain-like 'spiking' computational frameworks, neuromorphic computing-brain-inspired computing for machine intelligence-promises to realize artificial intelligence while reducing the energy requirements of computing platforms. This interdisciplinary field began with the implementation of silicon circuits for...


    pub_type: 杂志文章,评审


    authors: Roy K,Jaiswal A,Panda P

    更新日期:2019-11-01 00:00:00

  • Molecular machines governing exocytosis of synaptic vesicles.

    abstract::Calcium-dependent exocytosis of synaptic vesicles mediates the release of neurotransmitters. Important proteins in this process have been identified such as the SNAREs, synaptotagmins, complexins, Munc18 and Munc13. Structural and functional studies have yielded a wealth of information about the physiological role of ...


    pub_type: 杂志文章,评审


    authors: Jahn R,Fasshauer D

    更新日期:2012-10-11 00:00:00

  • Mesostructured germanium with cubic pore symmetry.

    abstract::Regular mesoporous oxide materials have been widely studied and have a range of potential applications, such as catalysis, absorption and separation. They are not generally considered for their optical and electronic properties. Elemental semiconductors with nanopores running through them represent a different form of...


    pub_type: 信件


    authors: Armatas GS,Kanatzidis MG

    更新日期:2006-06-29 00:00:00

  • Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.

    abstract::Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyl...


    pub_type: 杂志文章


    authors: Tanzi RE,McClatchey AI,Lamperti ED,Villa-Komaroff L,Gusella JF,Neve RL

    更新日期:1988-02-11 00:00:00

  • Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1.

    abstract::Segmentation of the vertebrate hindbrain into rhombomeres is important for the anterior-posterior arrangement of cranial motor nuclei and efferent nerves. Underlying this reiterated organization, Hox genes display segmentally restricted domains of expression, such as expression of Hoxb-1 (refs 5, 6) in rhombomere 4 (r...


    pub_type: 杂志文章


    authors: Studer M,Lumsden A,Ariza-McNaughton L,Bradley A,Krumlauf R

    更新日期:1996-12-19 00:00:00

  • A motif in the alphabeta T-cell receptor controls positive selection by modulating ERK activity.

    abstract::Positive selection allows thymocytes that recognize an individual's own major histocompatibility complex (self-MHC) molecules to survive and differentiate, whereas negative selection removes overtly self-reactive thymocytes. Although both forms of thymic selection are mediated by the alphabeta T-cell receptor (TCR) an...


    pub_type: 杂志文章


    authors: Werlen G,Hausmann B,Palmer E

    更新日期:2000-07-27 00:00:00

  • How AI and satellites could help predict volcanic eruptions.

    abstract:: ...


    pub_type: 杂志文章


    authors: Witze A

    更新日期:2019-03-01 00:00:00

  • A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus.

    abstract::Mice express a collection of superantigens, which bind to class II major histocompatibility proteins and interact with T cells bearing particular V beta chains as part of their alpha beta receptors. These superantigens have been suggested to be encoded by exogenous or endogenous mouse mammary tumour viruses. One such ...


    pub_type: 杂志文章


    authors: Choi Y,Kappler JW,Marrack P

    更新日期:1991-03-21 00:00:00

  • Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.

    abstract::Aberrant regulation of RNA stability has an important role in many disease states. Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types. A defining feature of RNA is its ability ...


    pub_type: 杂志文章


    authors: Goodarzi H,Zhang S,Buss CG,Fish L,Tavazoie S,Tavazoie SF

    更新日期:2014-09-11 00:00:00

  • Local-feature assembling in visual pattern recognition and generalization in honeybees.

    abstract::Generalization is a cognitive ability that allows similar stimuli along a given dimension to be treated as equivalents. Insects exhibit high levels of visual generalization. Honeybees trained to recognize complex visual stimuli on the basis of a single feature generalize their choice to novel stimuli sharing that comm...


    pub_type: 杂志文章


    authors: Stach S,Benard J,Giurfa M

    更新日期:2004-06-17 00:00:00

  • A uniquely specialized ear in a very early tetrapod.

    abstract::The Late Devonian genus Ichthyostega was for many decades the earliest known tetrapod, and the sole representative of a transitional form between a fish and a land vertebrate. However, despite being known since 1932 (ref. 1) from a large collection of specimens, its morphology remained enigmatic and not what was expec...


    pub_type: 杂志文章


    authors: Clack JA,Ahlberg PE,Finney SM,Dominguez Alonso P,Robinson J,Ketcham RA

    更新日期:2003-09-04 00:00:00

  • Spectroscopy of short-lived radioactive molecules.

    abstract::Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1-4. Radioactive molecules-in which one or more of the atoms possesses a radioactive nucleus-can contain heavy and deformed nuclei, offering high sensitivit...


    pub_type: 杂志文章


    authors: Garcia Ruiz RF,Berger R,Billowes J,Binnersley CL,Bissell ML,Breier AA,Brinson AJ,Chrysalidis K,Cocolios TE,Cooper BS,Flanagan KT,Giesen TF,de Groote RP,Franchoo S,Gustafsson FP,Isaev TA,Koszorús Á,Neyens G,Perrett HA

    更新日期:2020-05-01 00:00:00

  • Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.

    abstract::There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and...


    pub_type: 杂志文章


    authors: Guttman M,Amit I,Garber M,French C,Lin MF,Feldser D,Huarte M,Zuk O,Carey BW,Cassady JP,Cabili MN,Jaenisch R,Mikkelsen TS,Jacks T,Hacohen N,Bernstein BE,Kellis M,Regev A,Rinn JL,Lander ES

    更新日期:2009-03-12 00:00:00

  • East Antarctic rifting triggers uplift of the Gamburtsev Mountains.

    abstract::The Gamburtsev Subglacial Mountains are the least understood tectonic feature on Earth, because they are completely hidden beneath the East Antarctic Ice Sheet. Their high elevation and youthful Alpine topography, combined with their location on the East Antarctic craton, creates a paradox that has puzzled researchers...


    pub_type: 杂志文章


    authors: Ferraccioli F,Finn CA,Jordan TA,Bell RE,Anderson LM,Damaske D

    更新日期:2011-11-16 00:00:00

  • Biodiversity loss and its impact on humanity.

    abstract::The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nati...


    pub_type: 杂志文章,评审


    authors: Cardinale BJ,Duffy JE,Gonzalez A,Hooper DU,Perrings C,Venail P,Narwani A,Mace GM,Tilman D,Wardle DA,Kinzig AP,Daily GC,Loreau M,Grace JB,Larigauderie A,Srivastava DS,Naeem S

    更新日期:2012-06-06 00:00:00

  • Very mild muscular dystrophy associated with the deletion of 46% of dystrophin.

    abstract::Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), a much milder form of the disease where the age of onset can sometimes be as late as the third or fourth decade of life, are caused by mutations in the same X-linked gene, a 14 kilobase (kb) transcript which is spread over more than 2 megabases of ...


    pub_type: 杂志文章


    authors: England SB,Nicholson LV,Johnson MA,Forrest SM,Love DR,Zubrzycka-Gaarn EE,Bulman DE,Harris JB,Davies KE

    更新日期:1990-01-11 00:00:00

  • HIF-1α metabolically controls collagen synthesis and modification in chondrocytes.

    abstract::Endochondral ossification, an important process in vertebrate bone formation, is highly dependent on correct functioning of growth plate chondrocytes1. Proliferation of these cells determines longitudinal bone growth and the matrix deposited provides a scaffold for future bone formation. However, these two energy-depe...


    pub_type: 杂志文章


    authors: Stegen S,Laperre K,Eelen G,Rinaldi G,Fraisl P,Torrekens S,Van Looveren R,Loopmans S,Bultynck G,Vinckier S,Meersman F,Maxwell PH,Rai J,Weis M,Eyre DR,Ghesquière B,Fendt SM,Carmeliet P,Carmeliet G

    更新日期:2019-01-01 00:00:00

  • Apolipoprotein E controls cerebrovascular integrity via cyclophilin A.

    abstract::Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and i...


    pub_type: 杂志文章


    authors: Bell RD,Winkler EA,Singh I,Sagare AP,Deane R,Wu Z,Holtzman DM,Betsholtz C,Armulik A,Sallstrom J,Berk BC,Zlokovic BV

    更新日期:2012-05-16 00:00:00

  • Genetic information and life insurance.

    abstract::Genetic testing will become the future standard of medical care. Life insurers will also need access to genetic information if the insurance industry is to survive intact and if cover is to remain affordable. ...


    pub_type: 杂志文章


    authors: Pokorski RJ

    更新日期:1995-07-06 00:00:00

  • Supersolid symmetry breaking from compressional oscillations in a dipolar quantum gas.

    abstract::Supersolids are exotic materials combining the frictionless flow of a superfluid with the crystal-like periodic density modulation of a solid. The supersolid phase of matter was predicted 50 years ago1-3 for solid helium4-8. Ultracold quantum gases have recently been made to exhibit periodic order typical of a crystal...


    pub_type: 杂志文章


    authors: Tanzi L,Roccuzzo SM,Lucioni E,Famà F,Fioretti A,Gabbanini C,Modugno G,Recati A,Stringari S

    更新日期:2019-10-01 00:00:00

  • Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells.

    abstract::Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the h...


    pub_type: 杂志文章


    authors: Bao EL,Nandakumar SK,Liao X,Bick AG,Karjalainen J,Tabaka M,Gan OI,Havulinna AS,Kiiskinen TTJ,Lareau CA,de Lapuente Portilla AL,Li B,Emdin C,Codd V,Nelson CP,Walker CJ,Churchhouse C,de la Chapelle A,Klein DE,Nilsson

    更新日期:2020-10-01 00:00:00