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dc.contributor.authorGonzález-Gómez, P.
dc.contributor.authorCrecente-Campo, J.
dc.contributor.authorZahonero, C.
dc.contributor.authorDe La Fuente Freire, María 
dc.contributor.authorHernández-Laín, A.
dc.contributor.authorMira, H.
dc.contributor.authorSánchez-Gómez, P.
dc.contributor.authorGarcia-Fuentes, M.
dc.date.accessioned2017-06-07T07:35:06Z
dc.date.available2017-06-07T07:35:06Z
dc.date.issued2015
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/20.500.11940/8228
dc.description.abstractGlioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPdelta. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy.
dc.description.sponsorshipGobierno de España
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipXunta de Galicia
dc.description.sponsorshipComisión Europea
dc.description.sponsorshipBBVA Foundation
dc.description.sponsorshipMinisterio de Economia y Competitividad, Red Tematica de Investigacion Cooperativa en Cancer
dc.description.sponsorship"Sara Borell" postdoctoral fellowship
dc.description.sponsorshipInstituto de Salud Carlos III/PI12/101
dc.description.sponsorshipInstituto de Salud Carlos III/PI12/00775
dc.description.sponsorshipInstituto de Salud Carlos III/PS09/1786
dc.description.sponsorshipInstituto de Salud Carlos III/PI13/01258
dc.description.sponsorshipComunidad de Madrid/S2010/BMD-2336
dc.description.sponsorshipXunta de Galicia/European Commission/EM2013/042
dc.description.sponsorshipBBVA Foundation/2014-PO010
dc.description.sponsorshipMinisterio de Economia y Competitividad, Red Tematica de Investigacion Cooperativa en Cancer/RD12/0036/0027
dc.language.isoeng
dc.subject.meshAnimals
dc.subject.meshApoptosis
dc.subject.meshBlotting, Western
dc.subject.meshBone Morphogenetic Protein 7
dc.subject.meshBrain Neoplasms
dc.subject.meshCell Movement
dc.subject.meshCell Proliferation
dc.subject.meshDelayed-Action Preparations
dc.subject.meshGlioblastoma
dc.subject.meshHumans
dc.subject.meshImmunoenzyme Techniques
dc.subject.meshMice
dc.subject.meshMice, Nude
dc.subject.meshMicrospheres
dc.subject.meshRNA, Messenger
dc.subject.meshReal-Time Polymerase Chain Reaction
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshTumor Cells, Cultured
dc.subject.meshXenograft Model Antitumor Assays
dc.titleControlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma
dc.typeArtigoes
dc.authorsophosGonzález-Gómez, P.
dc.authorsophosCrecente-Campo, J.
dc.authorsophosZahonero, C.
dc.authorsophosde la Fuente, M.
dc.authorsophosHernández-Laín, A.
dc.authorsophosMira, H.
dc.authorsophosSánchez-Gómez, P.
dc.authorsophosGarcia-Fuentes, M.
dc.identifier.isi359006400023
dc.identifier.pmid25860932
dc.identifier.sophos19573
dc.issue.number13
dc.journal.titleOncotarget
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Oncoloxía médica
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago
dc.page.initial10950
dc.page.final10963
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number6


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