| First Author | Chen J | Year | 2012 |
| Journal | Nature | Volume | 488 |
| Issue | 7412 | Pages | 522-6 |
| PubMed ID | 22854781 | Mgi Jnum | J:186769 |
| Mgi Id | MGI:5433228 | Doi | 10.1038/nature11287 |
| Citation | Chen J, et al. (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488(7412):522-6 |
| abstractText | 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-DeltaTK-IRES-GFP (Nes-DeltaTK-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-DeltaTK-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. |
