Human glioma stem cells (GSC) : undifferentiated versus differentiated in presence or absence of active GSK3beta

ABSTRACT: Transcriptional profilling of human GSC comparing undifferentiated (ND) and differentiated (Diff 0.5%) GSC treated or not with TWS119 (LW) an inhibitor of GSK3beta Glioblastomas (GBM) are the most common form of primary brain tumors. Highly vascularized, infiltrating, resistant to current therapies, they affect patients at different ages. The median survival is shorter than 18 months. GBM follow the cancer stem cell (CSC) model. This concept proposes that a minority of cells within the tumor mass, with long term self-renewal and differentiation properties, is responsible for the initiation and the growth of tumors. CSCs provide all the subtypes of cells that compose the tumor, including endothelial cells and pericytes. Their functional properties are associated with a molecular signature combining makers of neural and/or embryonic stem cells, and markers of mesenchymal cells. A growing body of evidences supports that tumor’s behavior, including proliferation, progression, invasion and – most importantly - a great part of resistance to therapies are determined by these self-renewing tumor cells. It is becoming therefore evident that failure of current treatments to eliminate glioma-initiating cells (GiCs) contributes to tumor recurrence. Targeting GiCs and their stem-like properties constitutes thus one of the main therapeutic challenges to significantly improve anti-cancer treatments. A relevant solution to target GiCs, is to force them to acquire a non self-renewing state. Under this non stem-like state, the cells lose their tumorigenicity and become vulnerable to therapies. We observed that GiC differentiation is associated to an increase of active GSK3beta expression. Suppression of this activation using a chemical inhibitor (TWS119) altered the differentiation process. To identify transcroptomic changes due to GSK3beta inhibition during differentiation, we have differentiated two GiC cultures (TG1, and TG6) treated or not with TWS119. Total mRNA have been extracted and compared to mRNA extracted from self-renewing TG1 and TG6 cells. For these experiments we used “Agilent human genome whole 44K” chips. two-condition experiment, undifferentiated GSC (ND) vs. Differentiated (diff 0.5%) and undifferentiated GSC (ND) versus differentiated GSC treated with TWS119 (diff 0.5%LW) in monoplicate in TG1 and in TG6 cells (two different primary cultures of GSC).

ORGANISM(S): Homo sapiens

SUBMITTER: Thierry Girolle 

PROVIDER: E-GEOD-79478 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress