ISOLATION AND CHARACTERIZATION OF STEM CELLS ISOLATED FROM HUMAN LOW-GRADE AND HIGH-GRADE GLIOMAS

Low-grade gliomas (LGG)are characterized by a heterogeneous clinical behavior that is only partly foreseeable by the prognostic and predictive markers available, rendering difficult the decision- making process. Recently, the attention has been focused on the tumor microenviroment, believed to be of prognostic and predictive value, and possible novel drug-target. Therefore, the aim of the study was to isilated from LGG and high- grade gliomas (HGG)proliferating stem cell lines representative of the glioma stroma and to use this in-vitro model to identify novel prognostic markers. Methods: in this study multipotent adult stem cells, named glioma-associated stem cells (GASC) were isolated from LGG (n=40) and HGG (n=73). GASC were characterized by stem cell features, aberrant anchorage-independent growth, tumor-supporting ability and were devoid of the glioma mutations characterizing the respective tumor tissue, thus representing a population of glioma supporting stem cells. Starting from a case study composed of GASC obtained from HGG (n=13) and LGG (n=12) and utilizing a ROC analysis, we identified 9 GASC surface markers whose expression level could be utilized to correctly classify the two groups. Afterward we created a score based on the expression of these 9 significant parameters and we assayed its prognostic value in a casistic including 40 subsequent LGG-patients (median follow-up 36 months, range 13-76). At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival (HR 8.84, Cl 95% 2.15-36.28) and malignant progression free- survival (HR3.74,cl95% 1.60-8.75),out performing the state of the art histological, clinical and molecular LGG prognostic factors. Conclusions: it is possible to isolate from LGG and HGG cells endowed with strong prognostic information.