Year: 2013
Type: dissertation
Abstract: The TGF-beta oncogenic effect has been widely studied. In glioma, TGF-beta has an oncogenic role increasing cell proliferation and glioma-initiating cell (GIC) self-renewal capacity. During the investigation of this thesis, I have studied the oncogenic role of TGF-beta focusing in its action on GICs. First of all, we have characterized the population of GICs and its biomarkers CD44high/Id1+. We have demonstrated that this population has tumor initiating capacity in vivo and that they depend on the TGF-beta pathway activity, thus they can be targeted by inhibitors of TGF-beta. Furthermore, we have observed that this population CD44high/Id1+ tend to be located in a perivascular niche and we described that endothelial cells provide TGF-beta to the local microenvironment to maintain GICs properties such as self-renewal capacity and tumorigenic potential. One of the main characteristics of GICs is their resistance to conventional treatments such as radiotherapy. We observed an enrichment of CD44high/Id1+ GICs after radiotherapy. Targeting GICs with TGF-beta inhibitor radiosensitizes CD44high/Id1+ cells. \nOne important mediator of TGF-beta oncogenic effect is the transcription factor Runx1. Runx1 is necessary for LIF induction by TGF-beta, thus maintaining GICs self-renewal capacity and undifferentiated state. Furthermore, Runx1 is also necessary for the mesenchymal phenotype of GBM and for tumor formation in vivo. In glioma patients we observe that Runx1 levels correlate with tumor grade and overexpression of Runx1 is a poor-prognosis factor. \nThis is the first time we postulate that Runx1 is an important mediator of the TGF-beta oncogenic effect in glioma.
Author: Alba Gonzàlez Juncà
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W202291529