Farace, Cristiano (2014) Molecular and ultra-structural insight into the enrichment of Glioblastoma and Neuroblastoma stem-like cells. Doctoral Thesis.
Cancer stem cells (CSC) and tumor micro-environments play a significant role in malignant cancer initiation and progression. Metastasis in vivo involves a stem-like, epithelial-mesenchymal transition (EMT). Serum-free cultures of 3-D neurospheres represent the gold standard in CSC-like enrichment. The aim of the thesis was to explore the induction of stem-like phenotypes in Glioblastoma (GBM) and Neuroblastoma (NBL) cell lines, in order to assess common stem/oncogenic related marks. CSC characterization, Temozolomide (TMZ) treatments, TEM/SEM microscopy and comparative gene expression analysis (cDNA Microarray, qRT-PCR and WB) were conducted. High 3D spheres generation, TMZ resistance of induced cells, and ultrastructure of the spheres underlay the enrichment of both cell lines. Molecular analysis have shown small leucine-rich proteoglycans (SLRPs) decorin and lumican over-expression in neurospheres, SLRPs are bi-functional extracellular matrix (ECM)-related proteins involved in collagen fibers and signaling pathways modulations. Taken together, data observed in thesis suggest that CSC can modulate its cellular function and surrounding micro-environment (niches), by inducing SLRPs that play a crucial role in sphere cultures and in the modulation of stem and cancer-related pathways. Further functional studies are required to better understand their role in cancer, and clinical evaluations of SLRPs in GBM and NBL patients could lead to uncover their potential as clinical tools.
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