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

1035 Citations (Scopus)

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
StatePublished - Aug 23 2012

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Glioblastoma
temozolomide
Drug Therapy
Growth
Population
Neoplasms
Glioma
Nestin
Ganciclovir
Transgenes
Recurrence
Adult Stem Cells
Neural Stem Cells
Neoplastic Stem Cells
Lateral Ventricles
Brain Neoplasms
Cell Proliferation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

A restricted cell population propagates glioblastoma growth after chemotherapy. / Chen, Jian; Li, Yanjiao; Yu, Tzong Shiue; McKay, Renée M.; Burns, Dennis K.; Kernie, Steven G.; Parada, Luis F.

In: Nature, Vol. 488, No. 7412, 23.08.2012, p. 522-526.

Research output: Contribution to journalArticle

Chen, Jian ; Li, Yanjiao ; Yu, Tzong Shiue ; McKay, Renée M. ; Burns, Dennis K. ; Kernie, Steven G. ; Parada, Luis F. / A restricted cell population propagates glioblastoma growth after chemotherapy. In: Nature. 2012 ; Vol. 488, No. 7412. pp. 522-526.
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