Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma Journal Article

Authors: Barrett, L. E.; Granot, Z.; Coker, C.; Iavarone, A.; Hambardzumyan, D.; Holland, E. C.; Nam, H. S.; Benezra, R.
Article Title: Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma
Abstract: Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain self-renewal and multipotency of adult neural stem cells. Using PDGF- and KRAS-driven murine models of gliomagenesis, we show that high Id1 expression (Id1 high) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1 low) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1 low cells generate tumors more rapidly and with higher penetrance than Id1 high cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1 low cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression. © 2012 Elsevier Inc.
Keywords: platelet derived growth factor; cancer survival; controlled study; protein expression; gene deletion; nonhuman; glioma; cancer grading; cell proliferation; animal cell; mouse; inhibitor of differentiation 1; oligodendrocyte transcription factor 2; animal experiment; animal model; cell renewal; carcinogenesis; cell lineage; tumor cell; gene silencing; tumor growth; k ras protein; penetrance; cell self renewal
Journal Title: Cancer Cell
Volume: 21
Issue: 1
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2012-01-17
Start Page: 11
End Page: 24
Language: English
DOI: 10.1016/j.ccr.2011.11.025
PROVIDER: scopus
PUBMED: 22264785
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "CODEN: CCAEC" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Eric Holland
    224 Holland
  2. Robert Benezra
    144 Benezra
  3. Zvi Granot
    9 Granot
  4. Courtney Coker
    5 Coker
  5. Hyung-Song Nam
    7 Nam