A restricted cell population propagates glioblastoma growth after chemotherapy

Jian Chen, Yanjiao Li, Tzong Shiue Yu, Renée M. McKay, Dennis K. Burns, Steven G. Kernie, Luis F. Parada

Research output: Contribution to journalArticle

1096 Scopus citations

Abstract

Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year. 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-δTK-IRES-GFP (Nes-δTK-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-δTK-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.

Original languageEnglish (US)
Pages (from-to)522-526
Number of pages5
JournalNature
Volume488
Issue number7412
DOIs
Publication statusPublished - Aug 23 2012

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