A restricted cell population propagates glioblastoma growth after chemotherapy

Article

关键词: EXPRESSING PROGENITORS;    INITIATING CELLS;    MOUSE MODELS;    STEM-CELLS;    NEUROGENESIS;    GLIOMA;    ASTROCYTOMAS;    BRAIN;    RARE;   

DOI  :  10.1038/nature11287

来源: SCIE

【 摘 要 】

Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year(1). This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-Delta TK-IRES-GFP (Nes-Delta TK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-Delta TK-GFP transgene subpopulation. Ablation of the GFP(+) cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.

【 授权许可】

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