Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma
Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma
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DOI：
10.1016/j.ccr.2011.11.025
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发表时间：
2012-01-17
期刊：
影响因子：
50.3
通讯作者：
Benezra, Robert
中科院分区：
文献类型：
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作者：
Barrett, Lindy E.;Granot, Zvi;Benezra, Robert
在高级别胶质瘤中，干细胞样细胞的确切身份和功能作用仍不清楚。在正常的神经源性龛中，ID（DNA结合抑制剂）基因维持成体神经干细胞的自我更新和多能性。使用PDGF和KRAS驱动的胶质瘤发生小鼠模型，我们表明，高Id1表达（Id1（高））识别具有高自我更新能力的肿瘤细胞，而低Id1表达（Id1（低））识别具有增殖潜力但自我更新能力有限的肿瘤细胞。令人惊讶的是，Id1（低）细胞比Id1（高）细胞更快地产生肿瘤，并且具有更高的转移率。此外，通过缺失Id1消除肿瘤细胞自我更新对动物存活具有适度的影响，而Id1（低）细胞内Olig2的敲低具有显著的存活益处，强调了非自我更新谱系在疾病进展中的重要性。
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.