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dc.contributor.authorRodrigues-Ferreira, Sylvie
dc.contributor.authorAbdelkarim, Mohamed
dc.contributor.authorDillenburg-Pilla, Patricia
dc.contributor.authorLuissint, Anny-Claude
dc.contributor.authordi-Tommaso, Anne
dc.contributor.authorDeshayes, Frederique
dc.contributor.authorPontes, Carmen Lucia S.
dc.contributor.authorMolina, Angie
dc.contributor.authorCagnard, Nicolas
dc.contributor.authorLetourneur, Franck
dc.contributor.authorMorel, Marina
dc.contributor.authorReis, Rosana I.
dc.contributor.authorCasarini, Dulce Elena [UNIFESP]
dc.contributor.authorTerris, Benoit
dc.contributor.authorCouraud, Pierre-Olivier
dc.contributor.authorCosta-Neto, Claudio M.
dc.contributor.authorDi Benedetto, Melanie
dc.contributor.authorNahmias, Clara
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 7, n. 4, 8 p., 2012.
dc.description.abstractBreast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. in this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. in vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.en
dc.description.sponsorshipUniversity Paris Descartes
dc.description.sponsorshipCentre National de la Recherche Scientifique
dc.description.sponsorshipLigue Contre le Cancer-Comite Ile de France
dc.description.sponsorshipAssociation pour la Recherche contre le Cancer (ARC)
dc.description.sponsorshipFondation RAJA
dc.description.sponsorshipassociation Prolific
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsAcesso aberto
dc.titleAngiotensin II Facilitates Breast Cancer Cell Migration and Metastasisen
dc.contributor.institutionUniv Paris 05
dc.contributor.institutionUniv Paris 13
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.description.affiliationINSERM, Inst Cochin, Paris, France
dc.description.affiliationUniv Paris 05, Paris, France
dc.description.affiliationUniv Paris 13, Bobigny, France
dc.description.affiliationCNRS, UMRS 940, IGM, Paris, France
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto, Brazil
dc.description.affiliationUniv Fed Sao Carlos, Dept Physiol Sci, BR-13560 Sao Carlos, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
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