dc.contributor.author | Huang, Yujie | |
dc.contributor.author | Rajappa, Prajwal | |
dc.contributor.author | Hu, Wenhuo | |
dc.contributor.author | Hoffman, Caitlin | |
dc.contributor.author | Cisse, Babacar | |
dc.contributor.author | Kim, Joon-Hyung | |
dc.contributor.author | Gorge, Emilie | |
dc.contributor.author | Yanowitch, Rachel | |
dc.contributor.author | Cope, William | |
dc.contributor.author | Vartanian, Emma | |
dc.contributor.author | Xu, Raymond | |
dc.contributor.author | Zhang, Tuo | |
dc.contributor.author | Pisapia, David | |
dc.contributor.author | Xiang, Jenny | |
dc.contributor.author | Huse, Jason | |
dc.contributor.author | Matei, Irina | |
dc.contributor.author | Peinado Selgas, Hector | |
dc.contributor.author | Bromberg, Jacqueline | |
dc.contributor.author | Holland, Eric | |
dc.contributor.author | Ding, Bi-Sen | |
dc.contributor.author | Rafii, Shahin | |
dc.contributor.author | Lyden, David | |
dc.contributor.author | Greenfield, Jeffrey | |
dc.date.accessioned | 2019-09-30T09:36:34Z | |
dc.date.available | 2019-09-30T09:36:34Z | |
dc.date.issued | 2017-05-01 | |
dc.identifier.citation | J Clin Invest. 2017 ;127(5):1826-1838. | es_ES |
dc.identifier.issn | 0021-9738 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8388 | |
dc.description.abstract | Tumors 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | American Society for Clinical Investigation (ASCI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Granulocyte-Macrophage Colony-Stimulating Factor | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Inhibitor of Differentiation Protein 2 | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Transgenic | es_ES |
dc.subject.mesh | Neoplasm Proteins | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Transforming Growth Factor beta | es_ES |
dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-2 | es_ES |
dc.subject.mesh | Bone Marrow Cells | es_ES |
dc.subject.mesh | Glioma | es_ES |
dc.subject.mesh | Myeloid Cells | es_ES |
dc.subject.mesh | Neovascularization, Pathologic | es_ES |
dc.title | A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 28394259 | es_ES |
dc.format.volume | 127 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 1826-1838 | es_ES |
dc.identifier.doi | 10.1172/JCI86443 | es_ES |
dc.contributor.funder | Elizabeths Hope | |
dc.contributor.funder | Starr Foundation | |
dc.contributor.funder | Paduano Foundation | |
dc.contributor.funder | Champalimaud Foundation | |
dc.contributor.funder | Malcolm Hewitt Wiener Foundation | |
dc.contributor.funder | POETIC Foundation | |
dc.contributor.funder | Sohn Foundation | |
dc.contributor.funder | Hartwell Foundation | |
dc.contributor.funder | Children's Cancer and Blood Foundation | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1558-8238 | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/biomedicines6040105. | es_ES |
dc.identifier.journal | The Journal of clinical investigation | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Microambiente y Metástasis | es_ES |
dc.rights.accessRights | open access | es_ES |