Increasing evidence supports the idea of cancer as an aberrant morphogenetic process in which master developmental pathways (e.g. Hedgehog, Hh) are subverted. Stem cells (SC) sustain cell development through proliferation and differentiation events, from cell progenitor transitions until a fully differentiated phenotype. SC with similar properties have been also identified in most cancers. These cancer stem cells (CSC) may represent both the potential “cell of origin” of the tumor and a never ending reservoir responsible for tumor maintenance and progression. A paradigm of altered development as a cause of malignant transformation via aberrant Hh signaling is provided by Medulloblastoma (MB), the most common brain malignancy of childhood, in which also CSC have been described. Besides, microRNAs (miRNAs) have been recently identified as key molecules in the gene expression regulation both in development and in cancer: an altered expression of miRNAs is involved in neoplastic disorders and CSC behaviour. The overall aims of our work were to exploit the Hh-dependent tumorigenesis process of cerebellar stem/progenitor cells as a paradigmatic model to understand the link between subverted cell development and neoplastic transformation and tumor maintenance. We performed high-throughput miRNAs expression profiling of both neural and medulloblastoma stem cells (NSC, Mb SC). Of note, a number of miRNAs were found differentially expressed with stemness (both in NSC and in CSC). Moreover, we found different pattern of miRNAs expression in Mb SC samples in comparison with the normal counterpart (NSC). These observations suggest the presence of stemness specific and cancer stemness specific microRNA. Differentially expressed miRNAs will be selected for further testing on regulation of signaling pathways involved in the control of stemness and cell development. This study will provide new insight in miRNAs regulation and role in maintenance of the stem cell-like properties of neuronal tumor cells.
NEURAL STEM CELLS, CANCER STEM CELLS AND microRNAs:THE MEDULLOBLASTOMA PARADIGM
MIELE EConceptualization
;
2011-01-01
Abstract
Increasing evidence supports the idea of cancer as an aberrant morphogenetic process in which master developmental pathways (e.g. Hedgehog, Hh) are subverted. Stem cells (SC) sustain cell development through proliferation and differentiation events, from cell progenitor transitions until a fully differentiated phenotype. SC with similar properties have been also identified in most cancers. These cancer stem cells (CSC) may represent both the potential “cell of origin” of the tumor and a never ending reservoir responsible for tumor maintenance and progression. A paradigm of altered development as a cause of malignant transformation via aberrant Hh signaling is provided by Medulloblastoma (MB), the most common brain malignancy of childhood, in which also CSC have been described. Besides, microRNAs (miRNAs) have been recently identified as key molecules in the gene expression regulation both in development and in cancer: an altered expression of miRNAs is involved in neoplastic disorders and CSC behaviour. The overall aims of our work were to exploit the Hh-dependent tumorigenesis process of cerebellar stem/progenitor cells as a paradigmatic model to understand the link between subverted cell development and neoplastic transformation and tumor maintenance. We performed high-throughput miRNAs expression profiling of both neural and medulloblastoma stem cells (NSC, Mb SC). Of note, a number of miRNAs were found differentially expressed with stemness (both in NSC and in CSC). Moreover, we found different pattern of miRNAs expression in Mb SC samples in comparison with the normal counterpart (NSC). These observations suggest the presence of stemness specific and cancer stemness specific microRNA. Differentially expressed miRNAs will be selected for further testing on regulation of signaling pathways involved in the control of stemness and cell development. This study will provide new insight in miRNAs regulation and role in maintenance of the stem cell-like properties of neuronal tumor cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
