Publication:
Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.

Simple item page
dc.contributor.authorCosta-Silva, Bruno
dc.contributor.authorAiello, Nicole M
dc.contributor.authorOcean, Allyson J
dc.contributor.authorSingh, Swarnima
dc.contributor.authorZhang, Haiying
dc.contributor.authorThakur, Basant Kumar
dc.contributor.authorBecker, Annette
dc.contributor.authorHoshino, Ayuko
dc.contributor.authorMark, Milica Tešić
dc.contributor.authorMolina, Henrik
dc.contributor.authorXiang, Jenny
dc.contributor.authorZhang, Tuo
dc.contributor.authorTheilen, Till-Martin
dc.contributor.authorGarcía-Santos, Guillermo
dc.contributor.authorWilliams, Caitlin
dc.contributor.authorArarso, Yonathan
dc.contributor.authorHuang, Yujie
dc.contributor.authorRodrigues, Gonçalo
dc.contributor.authorShen, Tang-Long
dc.contributor.authorLabori, Knut Jørgen
dc.contributor.authorLothe, Inger Marie Bowitz
dc.contributor.authorKure, Elin H
dc.contributor.authorHernandez, Jonathan
dc.contributor.authorDoussot, Alexandre
dc.contributor.authorEbbesen, Saya H
dc.contributor.authorGrandgenett, Paul M
dc.contributor.authorHollingsworth, Michael A
dc.contributor.authorJain, Maneesh
dc.contributor.authorMallya, Kavita
dc.contributor.authorBatra, Surinder K
dc.contributor.authorJarnagin, William R
dc.contributor.authorSchwartz, Robert E
dc.contributor.authorMatei, Irina
dc.contributor.authorPeinado, Héctor
dc.contributor.authorStanger, Ben Z
dc.contributor.authorBromberg, Jacqueline
dc.contributor.authorLyden, David
dc.date.accessioned2024-02-12T12:56:12Z
dc.date.available2024-02-12T12:56:12Z
dc.date.issued2015-06
dc.description.abstractPancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden. Uptake of PDAC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PDAC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared with patients whose pancreatic tumours did not progress, MIF was markedly higher in exosomes from stage I PDAC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe thank D. L. Bajor (Vonderheide laboratory, University of Pennsylvania) for the gift of the R6560B cells. We thank L. Bojmar for carefully reviewing the paper. We thank S. Rudchenko and M. Barbu-Stevanovic at the Hospital for Special Surgery Fannie E. Rippel Foundation Flow Cytometry Core Facility for expert flow cytometry. We are supported by grants from the Children’s Cancer and Blood Foundation (H.P., D.L.), Manning Foundation (D.L.), Hartwell Foundation (D.L.), Champalimaud Foundation (D.L.), Fundacao para a Ciencia e a Tecnologia (D.L.), Nancy C and Daniel P Paduano Foundation (H.P., D.L.), Mary Kay Foundation (D.L.), Pediatric Oncology Experimental Therapeutic Investigator Consortium (D.L.), James Paduano Foundation (D.L., H.P.), Melanoma Research Alliance (H.P.), Sohn Conference Foundation (H.P.), Beth Tortolani Foundation (D.L., J.B.), Malcolm Hewitt Weiner Foundation (D.L.), Jose Carreras Leukemia Foundation (B.K.T.), Theodore Rapp Foundation (D.L.), American Hellenic Educational Progressive Association 5th District Cancer Research Foundation (D.L.), Charles and Marjorie Holloway Foundation (J.B.), Sussman Family Fund (J.B.), Lerner Foundation (J.B.), Breast Cancer Alliance (J.B.), and Manhasset Women’s Coalition Against Breast Cancer (J.B.).es_ES
dc.format.number6es_ES
dc.format.page816es_ES
dc.format.volume17es_ES
dc.identifier.citationNat Cell Biol . 2015;17(6):816-26es_ES
dc.identifier.doi10.1038/ncb3169es_ES
dc.identifier.e-issn1476-4679es_ES
dc.identifier.journalNature cell biologyes_ES
dc.identifier.pmchttp://hdl.handle.net/20.500.12105/17975
dc.identifier.pubmedID25985394es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/17975
dc.language.isoenges_ES
dc.publisherNature Publishing Group
dc.relation.publisherversionhttps://doi.org/10.1038/ncb3169.es_ES
dc.repisalud.institucionCNIOes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshAnimalses_ES
dc.subject.meshBase Sequencees_ES
dc.subject.meshBone Marrow Cellses_ES
dc.subject.meshCarcinoma, Pancreatic Ductales_ES
dc.subject.meshCell Line, Tumores_ES
dc.subject.meshCell Movementes_ES
dc.subject.meshExosomeses_ES
dc.subject.meshFemalees_ES
dc.subject.meshFibronectinses_ES
dc.subject.meshGene Expression Regulation, Neoplastices_ES
dc.subject.meshHepatic Stellate Cellses_ES
dc.subject.meshHumanses_ES
dc.subject.meshLiveres_ES
dc.subject.meshLiver Neoplasmses_ES
dc.subject.meshMacrophage Migration-Inhibitory Factorses_ES
dc.subject.meshMacrophageses_ES
dc.subject.meshMicees_ES
dc.subject.meshMice, Inbred C57BLes_ES
dc.subject.meshMice, Knockoutes_ES
dc.subject.meshPancreatic Neoplasmses_ES
dc.subject.meshPrecancerous Conditionses_ES
dc.subject.meshRNA Interferencees_ES
dc.subject.meshRNA, Small Interferinges_ES
dc.subject.meshSequence Analysis, RNAes_ES
dc.subject.meshSignal Transductiones_ES
dc.subject.meshTransforming Growth Factor betaes_ES
dc.titlePancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isPublisherOfPublication301fb00e-338e-4f8c-beaa-f9d8f4fefcc0
relation.isPublisherOfPublication.latestForDiscovery301fb00e-338e-4f8c-beaa-f9d8f4fefcc0

Files

Collections

Grupos de investigación