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Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression

Authors
 Hye-Min Jeon  ;  Sung-Hak Kim  ;  Xun Jin  ;  Jong Bae Park  ;  Se Hoon Kim  ;  Kaushal Joshi  ;  Ichiro Nakano  ;  Hyunggee Kim 
Citation
 CANCER RESEARCH, Vol.74(16) : 4482-4492, 2014 
Journal Title
 CANCER RESEARCH 
ISSN
 0008-5472 
Issue Date
2014
MeSH
Animals ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology* ; Cell Communication/physiology* ; Cell Differentiation/physiology ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Disease Progression ; Endothelial Cells/metabolism ; Endothelial Cells/pathology* ; Glioma/metabolism ; Glioma/pathology* ; Humans ; Mice ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Signal Transduction
Abstract
Glioma-initiating cells (GIC), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling crosstalk between GICs and endothelial cells are poorly understood. Here, we report that, in both GICs and endothelial cells, platelet-derived growth factor (PDGF)–driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor of differentiation 4 (ID4) expression, which in turn promotes JAGGED1–NOTCH activity through suppression of miR129 that specifically represses JAGGED1 suppression. This signaling axis promotes tumor progression along with increased GIC self-renewal and growth of tumor vasculature in the xenograft tumors, which is dramatically suppressed by NOTCH inhibitor. ID4 levels correlate positively with NOS2 (NO synthase-2), HES1, and HEY1 and negatively with miR129 in primary GICs. Thus, targeting the PDGF–NOS–ID4–miR129 axis and NOTCH activity in the perivascular microenvironment might serve as an efficacious therapeutic modality for glioblastoma.
Full Text
http://cancerres.aacrjournals.org/content/74/16/4482.long
DOI
10.1158/0008-5472.CAN-13-1597
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99482
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