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dc.contributor.authorHuang, Yujie
dc.contributor.authorRajappa, Prajwal
dc.contributor.authorHu, Wenhuo
dc.contributor.authorHoffman, Caitlin
dc.contributor.authorCisse, Babacar
dc.contributor.authorKim, Joon-Hyung
dc.contributor.authorGorge, Emilie
dc.contributor.authorYanowitch, Rachel
dc.contributor.authorCope, William
dc.contributor.authorVartanian, Emma
dc.contributor.authorXu, Raymond
dc.contributor.authorZhang, Tuo
dc.contributor.authorPisapia, David
dc.contributor.authorXiang, Jenny
dc.contributor.authorHuse, Jason
dc.contributor.authorMatei, Irina
dc.contributor.authorPeinado Selgas, Hector 
dc.contributor.authorBromberg, Jacqueline
dc.contributor.authorHolland, Eric
dc.contributor.authorDing, Bi-Sen
dc.contributor.authorRafii, Shahin
dc.contributor.authorLyden, David
dc.contributor.authorGreenfield, Jeffrey
dc.date.accessioned2019-09-30T09:36:34Z
dc.date.available2019-09-30T09:36:34Z
dc.date.issued2017-05-01
dc.identifier.citationJ Clin Invest. 2017 ;127(5):1826-1838.es_ES
dc.identifier.issn0021-9738es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8388
dc.description.abstractTumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-β and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas.es_ES
dc.description.sponsorshipThis study was supported by the Department of Defense Con- gressionally Directed Medical Research Programs (DOD CDMRP, CA120318 to Y. Huang), Elizabeth’s Hope (J. Greenfield), the Starr Foundation, the Paduano Foundation, the Champalimaud Foun- dation, the Malcolm Hewitt Wiener Foundation, the POETIC Foundation, the Sohn Foundation, the Hartwell Foundation, and the Children’s Cancer and Blood Foundation (all to D. Lyden). Address correspondence to: David Lyden, Department of Pediatrics, Weill Medical Medicine, 413 E. 69th Street, Box 284, New York, New York 10021, USA. Phone: 646.962.6238; E-mail: dcl2001@med.cornell.edu. Or to: Jeffrey P. Greenfield, Department of Neurological Surgery, Weill Cornell Medicine, 525 E 68th Street, Box 99, New York, New York 10065, USA. Phone: 212.746.2363; E-mail: jpgreenf@med.cornell.edu. HP’s present address is: Microenvironment and Metastasis Group, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.es_ES
dc.language.isoenges_ES
dc.publisherAMER SOC CLINICAL INVESTIGATION INCes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor es_ES
dc.subject.meshHumans es_ES
dc.subject.meshInhibitor of Differentiation Protein 2 es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Transgenic es_ES
dc.subject.meshNeoplasm Proteins es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshTransforming Growth Factor beta es_ES
dc.subject.meshVascular Endothelial Growth Factor Receptor-2 es_ES
dc.subject.meshBone Marrow Cells es_ES
dc.subject.meshGlioma es_ES
dc.subject.meshMyeloid Cells es_ES
dc.subject.meshNeovascularization, Pathologices_ES
dc.titleA proangiogenic signaling axis in myeloid cells promotes malignant progression of gliomaes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID28394259es_ES
dc.format.volume127es_ES
dc.format.number5es_ES
dc.format.page1826-1838es_ES
dc.identifier.doi10.1172/JCI86443es_ES
dc.contributor.funderElizabeth's Hopees_ES
dc.contributor.funderStarr Foundationes_ES
dc.contributor.funderPaduano Foundationes_ES
dc.contributor.funderChampalimaud Foundationes_ES
dc.contributor.funderMalcolm Hewitt Wiener Foundationes_ES
dc.contributor.funderPOETIC Foundationes_ES
dc.contributor.funderSohn Foundationes_ES
dc.contributor.funderHartwell Foundationes_ES
dc.contributor.funderChildren's Cancer and Blood Foundationes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1558-8238es_ES
dc.relation.publisherversionhttps://doi.org/10.3390/biomedicines6040105.es_ES
dc.identifier.journalThe Journal of clinical investigationes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Microambiente y Metástasises_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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