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

doi:10.1016/j.ccr.2011.11.025

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 journal › Article › peer-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 (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.

Original language	English
Pages (from-to)	11-24
Number of pages	14
Journal	Cancer Cell
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2011.11.025
State	Published - 17 Jan 2012
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2011.11.025

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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 (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.",

author = "Barrett, \{Lindy E.\} and Zvi Granot and Courtney Coker and Antonio Iavarone and Dolores Hambardzumyan and Holland, \{Eric C.\} and Nam, \{Hyung song\} and Robert Benezra",

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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doi = "10.1016/j.ccr.2011.11.025",

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AU - Barrett, Lindy E.

AU - Granot, Zvi

AU - Coker, Courtney

AU - Iavarone, Antonio

AU - Hambardzumyan, Dolores

AU - Holland, Eric C.

AU - Nam, Hyung song

AU - Benezra, Robert

N1 - 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.).

PY - 2012/1/17

Y1 - 2012/1/17

N2 - 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.

AB - 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.

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

Abstract

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