First Author | Barrett LE | Year | 2012 |
Journal | Cancer Cell | Volume | 21 |
Issue | 1 | Pages | 11-24 |
PubMed ID | 22264785 | Mgi Jnum | J:180283 |
Mgi Id | MGI:5306058 | Doi | 10.1016/j.ccr.2011.11.025 |
Citation | Barrett LE, et al. (2012) Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma. Cancer Cell 21(1):11-24 |
abstractText | 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. |