Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma

被引：113

作者：

Barrett, Lindy E. ^{[1
]}

Granot, Zvi ^{[1
]}

Coker, Courtney

Lavarone, Antonio ^{[2
]}

Hambardzumyan, Dolores ^{[3
]}

Holland, Eric C. ^{[1
]}

Hyung-song Nam ^{[1
]}

Benezra, Robert ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA

[2] Columbia Univ, Med Ctr, Dept Neurol, Inst Canc Genet, New York, NY 10032 USA

[3] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA

来源：

CANCER CELL | 2012年 / 21卷 / 01期

关键词：

CENTRAL-NERVOUS-SYSTEM; LOOP-HELIX PROTEINS; NEURAL STEM-CELLS; PROGENITORS; ORIGIN; OLIG2; ID1; IDENTIFICATION; EXPRESSION; PATHWAYS;

D O I：

10.1016/j.ccr.2011.11.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：11 / 24

页数：14

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