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

Lindy E. Barrett, Zvi Granot, Courtney Coker, Antonio Iavarone, Dolores Hambardzumyan, Eric C. Holland, Hyung song Nam, Robert Benezra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

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 (Id1high) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1low) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1low cells generate tumors more rapidly and with higher penetrance than Id1high cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1low cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression.

Original languageAmerican English
Pages (from-to)11-24
Number of pages14
JournalCancer Cell
Volume21
Issue number1
DOIs
StatePublished - 17 Jan 2012
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank members of the Benezra laboratory; E. Fomchenko, K. Pitter, and T. Ozawa for technical advice and reagents; The Laboratory of Comparative Pathology, Flow Cytometry Core Facility and Molecular Cytology Core Facility (MSKCC). Funding was provided through the Brain Tumor Center, MSKCC (L.E.B.), Ladies Auxiliary to the Veterans of Foreign Wars Postdoctoral Cancer Research Fellowship (L.E.B.), and the Kleberg Foundation (R.B.).

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