Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

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dc.contributor.authorMontecinos, Viviana P.
dc.contributor.authorGodoy, Alejandro
dc.contributor.authorHinklin, Jennifer
dc.contributor.authorVethanayagam, R. Robert
dc.contributor.authorSmith, Gary J.
dc.date.accessioned2024-01-10T12:41:46Z
dc.date.available2024-01-10T12:41:46Z
dc.date.issued2012
dc.description.abstractCharacterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for alpha-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts.
dc.description.funderNational Institutes of Health
dc.description.funderDepartment of Defense
dc.description.funderNational Cancer Institute Cancer Center
dc.description.funderNATIONAL CANCER INSTITUTE
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent13 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.pone.0029623
dc.identifier.issn1932-6203
dc.identifier.pubmedidMEDLINE:22303438
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0029623
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77449
dc.identifier.wosidWOS:000301770700005
dc.information.autorucMedicina;Montecinos V;S/I;111594
dc.issue.numero1
dc.language.isoen
dc.nota.accesoSin adjunto
dc.publisherPUBLIC LIBRARY SCIENCE
dc.revistaPLOS ONE
dc.rightsregistro bibliográfico
dc.subjectENDOTHELIAL GROWTH-FACTOR
dc.subjectRAT VENTRAL PROSTATE
dc.subjectBLOOD-VESSELS
dc.subjectIN-VIVO
dc.subjectRADICAL PROSTATECTOMY
dc.subjectANDROGEN DEPRIVATION
dc.subjectCANCER PROGRESSION
dc.subjectCELL PROLIFERATION
dc.subjectTUMOR ANGIOGENESIS
dc.subjectVEGF
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePrimary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma
dc.typeartículo
dc.volumen7
sipa.codpersvinculados111594
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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