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Eva Galan studies, with immunofluorescence and confocal microscopy, the expression of stem cell markers within neurospheres.

Glioblastoma multiforme may derive from a reservoir of glioblastoma stem-like cells (GSCs) that play a critical role in tumor resistance to treatments. At Institut Cochin, an ARC-funded post-doctorate, Eva Maria Galan Moya, is looking for new therapeutic targets by decrypting the endothelial factors contributing to the preservation of GSCs.

Eva Maria Galan Moya, a native of Albacete (Spain), has “always wanted to be a scientist". In 2010, she obtains brilliantly her PhD title in Experimental Biomedicine and the University of Castilla-La Mancha rewards her with an Extraordinary Award for her works on the resistance mechanisms to the anti-tumoral drug cisplatin [1]. Cancer had become her field of interest.

After a decisive encounter with Dr Julie Gavard* at the NIH in 2007, she joins in April 2010 her international research group “Vascular niche and tumor micro-environment” within the department Endocrinology, Metabolism and Cancer of the Institut Cochin, thanks to a 36-month grant provided by the ARC to post-doctorate students in France (“aide individuelle jeunes chercheurs”).  

As Eva Galan comments, “being a recipient of an ARC postdoctoral fellowship allowed me to move from Spain to France and to progress on a challenging project. In fact, the emergence of the “cancer stem cell hypothesis” has had a profound effect on the way I think about cancer. Thus, I decided to further centre my studies on investigating the tumor stem-like population and their microenvironment, also called “vascular niche”, particularly in glioblastoma”.

Glioblastoma multiforme (GBM) is the most frequent and malignant primary tumor of the central nervous system in adults. The cancer stem cell hypothesis proposes that GBM derive from a small reservoir of self-sustaining glioblastoma stem-like cells (GSCs). By inducing angiogenesis, tumor invasion and establishing drug resistance, GSCs may account for the failure of current treatments.  

GSCs are also closely associated to the endothelial cells (EC) of the brain vasculature within a specific and confined microenvironment. Besides its nutritive function, this vascular niche likely plays a crucial role in maintaining the renewal and integrity of GSCs. The ARC funding allowed the young scientist to look at the molecular mechanisms deployed by EC to sustain the GSC population.  

Eva Galan used four patient-derived GSCs that aggregate within neurospheres, which represent a good alternative to in vivo studies.  By looking at neurospheres formation and expression of stem cell markers such as Nestin and Sox-2 (as shown in Figure 1), she revealed that a brain endothelial secretome positively controls the expansion and survival of GSCs. The mammalian target of rapamycin (mTOR) signaling axis is active and vital to preserve the stemness identity of these cells.  Strikingly, it seems to be the target of these endothelial secreted factors (Figure 2and [2]).

The whereabouts of the dialogue between EC and GSC, as revealed by Eva and others, got reviewed in [3]. The scientist is currently exploring further the nature of the factors involved: “Proteomic analyses have allowed us to identify several secreted factors and confirm their essential role in the maintenance of the GSC phenotype”.  

Eva Galan got acknowledged for her work as "The interview of the day" by the Spanish medical journal "Diario Médico", since her findings offer wide therapeutic opportunities: “Targeting GSC population by hindering the endothelial signals critical for its integrity may indeed represent a relevant opportunity to identify treatments that selectively target the malignant niches and would make glioblastoma more susceptible to conventional therapies.” Eva Galan is highly decided to pursue her project in her current laboratory before starting to coordinate her own team.

A.G.

[1] Galan-Moya et al, Plos One 2011

[2] Galan-Moya et al, EMBO Rep 2011

[3] Galan-Moya and Gavard, J. Cell Cycle 2011

*Julie Gavard just got rewarded with the bronze medal of CNRS 2012 for her work on Kaposi Sarcomas. For this project, she also obtained in 2010 a 24-month ARC grant “subvention fixe”.

Credits photos: Eva María Galan Moya