Transforming growth factor-β mimics the key proteome properties of CD133- differentiated and CD133+ cancer stem cells in glioblastoma.

Abstract Glioblastoma multiforme is the most aggressive type of primary brain tumor in humans. Its invasive growth is associated with cluster of differentiation (CD)133 cancer stem cells (CSCs) and CD133− differentiated glioblastoma cells (DGCs) with aggressive phenotype, which are developed under the influence of transforming growth factor (TGF)-β. The present study aimed to compare the proteomes of CD133 CSCs and CD133− DGCs stimulated by TGF-β, as well as the expression levels of the main proteins responsible for activating the signaling pathway of receptor interactions with the extracellular matrix (ECM). The U87MG GBM cell line was used in this study. CSCs were extracted from gliomaspheres through magnetic-activated cell sorting based on the expression of CD133 (CD133); CD133− DCGs served as a control. CD133− DGCs of the U87-MG cell line were treated with 10 ng/mL TGF-β1, and cell proliferation and migration were analyzed via real-time quantitative microscopy. High-performance liquid chromatography mass spectrometry was used for proteome analysis. The results revealed 589 proteins with significantly changes in expression among CD133 CSCs compared with those in CD133− DGCs (P   twofold, while four proteins activated this signaling cascade. TGF-β-stimulation increased the mobility, suppressed the proliferation and transformed the proteome profile of CD133− DGCs. Were identified 13 key proteins that activate the signaling pathway of receptor interaction with the ECM and three proteins activating this signaling pathway in CD133− DGCs which had the same values as those of CD133 CSCs. In conclusion, TGF-β increased the expression of proteins that activate the signaling pathway of receptor interaction with the ECM in CD133− DGCs to the level of those in CD133 CSCs.