88 Meiliang Road, Wuxi Biopark phase 2, building 7
题目: The Stem of Gliomas:Malignant Gliomas Originate from Neural Stem/Progenitor Cells and are Maintained by “Cancer Stem Cells”
地点：909号楼一楼B会议室(Conference Room B, 909-1F)
Malignant astrocytomas are infiltrative and incurable brain tumors. Despite profound therapeutic implications, the identity of the cell (or cells) of origin has not been rigorously determined. We previously reported mouse models based on conditional inactivation of the human astrocytoma-relevant tumor suppressors p53, Nf1, and Pten, wherein through somatic loss of heterozygosity, mutant mice develop tumors with 100% penetrance. In the present study, we show that tumor suppressor inactivation in neural stem/progenitor cells is both necessary and sufficient to induce astrocytoma formation.
The median survival for grade IV gliomas is only about 1 year, which is mostly due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using our engineered mouse model of glioma, we have identified 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-DTKIRES-GFP (Nes-DTK-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 theNes-DTK-GFPtransgene 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.