Glioblastoma (GBM) tumor is the most aggressive and heterogeneous cancer originating from the Central Nervous System (CNS). It is not clear how this tumor heterogeneity comes about. The cancer stem cells (CSCs) theory dictates that GBM tumors may arise from a small pool of cells that determine the cancer progression. In this work, we demonstrate that isolated CSCs from single GBM-derived neurospheres give rise to several clones with different proliferation rates in vitro. Moreover, the tumors generated by xenografts of these clones, displayed histological features of GBM with different growth rates, which reflect the proliferation kinetics of the injected clones. These results indicate that exist differences in the tumorigenic capacity of CSCs derived from the same single neurosphere, suggesting a possible combination of the cancer stem cells hypothesis and clonal evolution model in generating GBM heterogeneity. We than investigated these differences as possibly related to the distinct expression of transcription factors NRSF/REST and Olig2, the equilibrium of which seems to maintain the more aggressive clone in the more tumorigenic status. Our results indicate a possible predictive role of REST since it is up regulated in more proliferative, invasive and less differentiated cells.

Cancer Stem Cells Recapitulates the Heterogeneity of Glioblastomas / F. Colleoni, M. Belicchi, P. Razini, M. Meregalli, R. Galli, S. Mazzoleni, S. Brunelli, M. Di Segni, D. Coviello, M. Baccarin, B. Pollo, N. Bresolin, L. Bello, L. Conti, Y. Torrente. - In: Journal of Stem Cell Research & Therapeutics. - 1:1(2015 Sep 18), pp. 26-37. [10.15406/jsrt.2015.01.00006]

Cancer Stem Cells Recapitulates the Heterogeneity of Glioblastomas.

F. Colleoni;M. Belicchi;M. Meregalli;N. Bresolin;L. Bello;Y. Torrente
2015-09-18

Abstract

Glioblastoma (GBM) tumor is the most aggressive and heterogeneous cancer originating from the Central Nervous System (CNS). It is not clear how this tumor heterogeneity comes about. The cancer stem cells (CSCs) theory dictates that GBM tumors may arise from a small pool of cells that determine the cancer progression. In this work, we demonstrate that isolated CSCs from single GBM-derived neurospheres give rise to several clones with different proliferation rates in vitro. Moreover, the tumors generated by xenografts of these clones, displayed histological features of GBM with different growth rates, which reflect the proliferation kinetics of the injected clones. These results indicate that exist differences in the tumorigenic capacity of CSCs derived from the same single neurosphere, suggesting a possible combination of the cancer stem cells hypothesis and clonal evolution model in generating GBM heterogeneity. We than investigated these differences as possibly related to the distinct expression of transcription factors NRSF/REST and Olig2, the equilibrium of which seems to maintain the more aggressive clone in the more tumorigenic status. Our results indicate a possible predictive role of REST since it is up regulated in more proliferative, invasive and less differentiated cells.
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/327453
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