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김은희

Kim, Eunhee
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Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity

Author(s)
Kim, YoungmiKim, EunheeWu, QiulianGuryanova, OlgaHitomi, MasahiroLathia, Justin D.Serwanski, DavidSloan, Andrew E.Weil, Robert J.Lee, JeongwuNishiyama, AkikoBao, ShidengHjelmeland, Anita B.Rich, Jeremy N.
Issued Date
2012-06
DOI
10.1101/gad.193565.112
URI
https://scholarworks.unist.ac.kr/handle/201301/20174
Fulltext
http://genesdev.cshlp.org/content/26/11/1247
Citation
GENES & DEVELOPMENT, v.26, no.11, pp.1247 - 1262
Abstract
Growth factor-mediated proliferation and self-renewal maintain tissue-specific stem cells and are frequently dysregulated in cancers. Platelet-derived growth factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors, as proven in genetically engineered models. While PDGFR alpha alterations inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral GBM heterogeneity. We found that PDGFR alpha is expressed only in a subset of GBMs, while PDGFR beta is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or pharmacological targeting of PDGFR beta (but not PDGFR alpha) attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFR beta inhibition decreased activation of the cancer stem cell signaling node STAT3, while constitutively active STAT3 rescued the loss of GSC self-renewal caused by PDGFR beta targeting. In silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor. Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies
Publisher
COLD SPRING HARBOR LAB PRESS
ISSN
0890-9369
Keyword (Author)
PDGFR betaStat3cancer stem cellglioblastomainvasion
Keyword
TUMOR-INITIATING CELLSCANCER STEM-CELLSHUMAN GLIOBLASTOMAFACTOR PDGFLUNG-CANCERSUBVENTRICULAR ZONEGLIAL TUMORIGENESISIONIZING-RADIATIONENDOTHELIAL-CELLSSELF-RENEWAL

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