Dr. Weeks’ Comment: Cancer STEM cells need to be appreciated. What you don’t know (about cancer STEM cells) can kill you.
A restricted cell population propagates glioblastoma growth after chemotherapy
Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year1. 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-Î”TK-IRES-GFP(Nes-Î”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-Î”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.
Nature. 2012 Aug 23;488(7412):522-6.
A restricted cell population propagates glioblastoma growth after chemotherapy.
Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF.
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.