Dissemination of proneural brain cancer cells: im.. (Dcxglioma)
Dissemination of proneural brain cancer cells: implication of partial and reversible differentiation into Dcx+ cells
Start date: Jul 1, 2012,
End date: Jun 30, 2014
Gliomas describe a range of devastating and progressive brain tumours affecting around 25000 people each year in Europe. Glioblastomas represent the most severe and frequent form of gliomas. A major finding in the field of glioblastomas is the recent identification of cancer stem cells within the tumour, holding a high tumorigenic potential. Those stem cell-like cancer cells are multipotent and resistant to radio- and chemotherapy, and are thus very likely to be responsible for the tumour recurrence after surgical resection. They possess as well high migratory properties, strongly understudied so far. Their anarchic dispersion through the parenchyma of patients represents the main hurdle to surgical resection therapy, and their ability to re-generate a tumour threatens the therapeutic outcome. That is why a deep understanding of the mechanisms preferentially borrowed by glioma stem cells to spread and survive should lead to adapted therapeutic strategies. This project is based on the original discovery by JP Hugnot’s group that glioma cells can spontaneously express the neuroblast marker Dcx to enter a migratory program in vitro, and in vivo. Interestingly, Dcx+ and Dcx- glioma cells from the same culture share different migratory and tumorigenic properties. This project aims at deciphering the respective intrinsic properties of Dcx+ and Dcx- gliomas cells in terms of migration and tumorigenicity, and to identify which molecular pathways influence these properties (with a focus on Notch and Shh based on preliminary data). For that, several resources are already available and in Pr Hugnot’s group: cell sorting, gliomas cell lines reportering the expression of Dcx (Gli4 pDcx-GFP), migration assays, cell transplantation of Dcx+ or Dcx- cells in the brain of nude mice.When further developed, these results will provide a substantial advance in the field of brain cancer research, and will open up significant therapeutic perspectives for the treatment of gliomas.
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