Evidence map›Paper›PMID 26524530›Full record

ArticleNature2015

Tumour exosome integrins determine organotropic metastasis.

Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen, Goncalo Rodrigues, Ayako Hashimoto, Milica Tesic Mark, Henrik Molina, Shinji Kohsaka, Angela Di Giannatale, Sophia Ceder and 44 more

Expression of concern Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. It is linked to trial NCT07224802 (An Exosome-based Liquid Biopsy Signature for Preoperative Identification of Occult Liver Metastasis in Patients With Pancreatic Ductal Adenocarcinoma), which is not on this map. Cited by 3,085 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3,085citing papers in PubMed, 2 pooled it
150.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07224802 completednot on this mapstarted 2024, after this paper: background citation

An Exosome-based Liquid Biopsy Signature for Preoperative Identification of Occult Liver Metastasis in Patients With Pancreatic Ductal Adenocarcinoma

TypeobservationalSponsorCity of Hope Medical CenterRan2024 to 2026Enrolled372ConditionsPDAC - Pancreatic Ductal AdenocarcinomaArmsEXELiM assay (qRT-PCR validation), EXELiM small RNA sequencing
3 · Its place in the literature

Who cites it

3,085 citing papers in PubMed, 2 syntheses or guidelines pooled it, 4,961 citations in OpenAlex.

  1. Pooled it
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  7. Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026
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3,025 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

54 authors at 15 institutions in 7 countries.

Ayuko HoshinoChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Bruno Costa-SilvaChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Tang-Long ShenChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Goncalo RodriguesChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Ayako HashimotoChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Milica Tesic MarkProteomics Resource Center, The Rockefeller University, New York, New York 10065, USA.
Henrik MolinaProteomics Resource Center, The Rockefeller University, New York, New York 10065, USA.
Shinji KohsakaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Angela Di GiannataleChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Sophia CederDepartment of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.
Swarnima SinghChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Caitlin WilliamsChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Nadine SoplopElectron Microscopy Resource Center (EMRC), Rockefeller University, New York, New York 10065, USA.
Kunihiro UryuElectron Microscopy Resource Center (EMRC), Rockefeller University, New York, New York 10065, USA.
Lindsay PharmerBreast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.
Tari KingBreast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.
Linda BojmarChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Alexander E DaviesLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Yonathan ArarsoChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Tuo ZhangGenomics Resources Core Facility, Weill Cornell Medicine, New York, New York 10021, USA.
Haiying ZhangChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Jonathan HernandezChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Joshua M WeissChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Vanessa D Dumont-ColeDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Kimberly KramerDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Leonard H WexlerDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Aru NarendranDivision of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada.
Gary K SchwartzDivision of Hematology/Oncology, Columbia University School of Medicine, New York, New York 10032, USA.
John H HealeyOrthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Per SandstromDepartment of Surgery, County Council of Östergötland, and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58185 Linköping, Sweden.
Knut Jørgen LaboriDepartment of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Nydalen, Oslo 0424, Norway.
Elin H KureDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Nydalen, Oslo 0424, Norway.
Paul M GrandgenettEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Michael A HollingsworthEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Maria de SousaChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Sukhwinder KaurDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Maneesh JainDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Kavita MallyaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
William R JarnaginDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Mary S BradyChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Oystein FodstadDepartment of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Nydalen, Oslo 0424, Norway.
Volkmar MullerDepartment of Gynecology, University Medical Center, Martinistrasse 52, 20246 Hamburg, Germany.
Klaus PantelDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Andy J MinnDepartment of Radiation Oncology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Mina J BissellLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Benjamin A GarciaDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Yibin KangDepartment of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Vinagolu K RajasekharBreast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Cyrus M GhajarFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Irina MateiChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Hector PeinadoChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Jacqueline BrombergDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
David LydenChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA.
Cornell University · USChildren's Cancer and Blood Foundation · USUniversity of Nebraska Medical Center · USMemorial Sloan Kettering Cancer Center · USLawrence Berkeley National Laboratory · USRockefeller University · USFred Hutch Cancer Center · USKarolinska Institutet · SEOslo University Hospital · NOPrinceton University · USThe University of Tokyo · JPUniversität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Pennsylvania · USWeill Cornell Medicine · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Characterization and Functional Analysis of Breast Cancer Secreted Exosomes in MaU01CA169538 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI BISSELL, MINA, LYDEN, DAVID CHARLES · 2012 to 2016
$2.9M
Exosome-mediated Transfer of c-MET to Bone Marrow Progenitors Promotes MetastasisR01CA169416 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LYDEN, DAVID CHARLES, PEINADO, HECTOR · 2013 to 2017
$1.7M
Critical Resources Provided by UNMC Rapid Autopsy Program (RAP) Biorepository Stimulate Cancer ResearchR50CA211462 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Paul M Grandgenett · 2016 to 2026
$1.4M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA169416NCI NIH HHS R01-CA169416NCI NIH HHS R50 CA211462NCI NIH HHS U01 CA169538NCI NIH HHS U01-CA169538
6 · The paper itself

Abstract

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.

Indexed as

TropismAnimalsBiomarkersBrainCell Line, TumorEndothelial CellsEpithelial CellsExosomesFemaleFibroblastsGenes, srcHumansIntegrin alpha6beta1Integrin alpha6beta4Integrin beta4Integrin beta ChainsBiomarkersIntegrin alpha6beta1Integrin alpha6beta4integrin alphaVbeta5Integrin beta4integrin beta5Integrin beta ChainsIntegrinsReceptors, VitronectinS100 Proteins

Identifiers

PMID26524530
PMCPMC4788391
OpenAlexW1950118853

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.