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

Research output: Contribution to journalArticlepeer-review

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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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