The Glioblastoma Multiforme (GBM) is a highly aggressive glial tumor, with a high recurrence and death rates. Recent studies indicate that the GBM is maintained by a sub-population of cells with stem-cells characteristics, denominated Glioblastoma Stem Cells (GSCs). Recently our group has identified the Cellular Prion Protein as having an important role in the modulation of the GSCs undifferentiated state. Our group has described the role of the Protein Prion Celular in the biology of the GSC, being involved in the modulation of proliferation and self-renewal of those cells. The PrPC is a GPI-anchored protein, capable of acting as a scaffold protein, forming complexes with multiple proteins, such as stemness markers. Also, PrPC loss-of-function inhibits GSCs self-renewal, proliferation and tumor initiating capabilities. A potential ligand of PrPC is CD44, a well known glycoprotein implicated in cellular adhesion and migration processes of GSCs Studies have shown the capacity of Neural Stem Cells to reduce stem-like phenotypes in GSCs, induce its differentiation and suppress tumor growth in vivo. Extracellular vesicles had been recognized as intercellular messengers implicated in the transfer of distinct molecules, including miRNA, to modify the phenotype of recipient cell. Remarkably, PrPC plays a role in exosomes modulating their secretion level through a caveolin dependant complex that drives autophagosome formation. Furthermore, a CD44 variant (CD44v6) is also related to the EVs in cancer, being a main component of exosomes in different types of tumor, participating in the stem-cells phenotype regulation. With that in mind, the aim of this project is to study the potential capacity EVs derived from NSCs might have in promoting differentiation in GSCs. (AU)
News published in Agência FAPESP Newsletter about the scholarship:
ALVES, RODRIGO NUNES;
IGLESIA, REBECA PIATNICZKA;
PRADO, MARIANA BRANDAO;
MELO ESCOBAR, MARIA ISABEL;
BOCCACINO, JACQUELINE MARCIA;
FERNANDES, CAMILA FELIX DE LIMA;
COELHO, BARBARA PARANHOS;
FORTES, AILINE CIBELE;
LOPES, MARILENE HOHMUTH.
A New Take on Prion Protein Dynamics in Cellular Trafficking.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,
Web of Science Citations: 0.
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