Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma.
Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma.
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DOI：
10.1101/sqb.2016.81.030973
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Parada LF
中科院分区：
文献类型：
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作者：
Alcantara Llaguno SR;Xie X;Parada LF
多形性胶质母细胞瘤（GBM）的细胞起源和进展机制、致瘤性的维持和治疗抗性是GBM领域的中心问题。利用肿瘤抑制小鼠模型，我们小组最近报道了两个独立的成年GBM起始中枢神经系统祖细胞群体。我们发现不同的功能和分子亚型取决于肿瘤起始细胞谱系，表明起源细胞是GBM亚型多样性的驱动因素。使用体内模型，我们还表明GBM癌症干细胞（CSC）或胶质瘤干细胞（GSC）有助于对化疗药物的耐药性，并且GSC的基因消融会导致肿瘤进展延迟。这些研究与起源细胞和CSC作为GBM发病机制的关键调节剂一致。
The cellular origins and the mechanisms of progression, maintenance of tumorigenicity, and therapeutic resistance are central questions in the glioblastoma multiforme (GBM) field. Using tumor suppressor mouse models, our group recently reported two independent populations of adult GBM-initiating central nervous system progenitors. We found different functional and molecular subtypes depending on the tumor-initiating cell lineage, indicating that the cell of origin is a driver of GBM subtype diversity. Using an in vivo model, we also showed that GBM cancer stem cells (CSCs) or glioma stem cells (GSCs) contribute to resistance to chemotherapeutic agents and that genetic ablation of GSCs leads to a delay in tumor progression. These studies are consistent with the cell of origin and CSCs as critical regulators of the pathogenesis of GBM.