The role of neural stem cells extracellular vesicles in the modulation of phenotype of PRNP low and PRNP high glioblastoma stem cells

• Grant number: 20/04687-4
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2020
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Rodrigo Nunes Alves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy, AP.JP2

Abstract

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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, v. 21, n. 20, OCT 2020. (20/07450-5, 17/26158-0, 19/14952-0, 19/11097-1, 20/04687-4, 18/15557-4, 19/12710-9, 19/14741-9)

COELHO, BARBARA PARANHOS; DE LIMA FERNANDES, CAMILA FELIX; BOCCACINO, JACQUELINE MARCIA; DA SILVA SOUZA, MARIA CLARA; MELO-ESCOBAR, MARIA ISABEL; ALVES, RODRIGO NUNES; PRADO, MARIANA BRANDAO; IGLESIA, REBECA PIATNICZKA; CANGIANO, GIOVANNI; MAZZARO, GIULIA LA ROCCA; et al. Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma. FRONTIERS IN ONCOLOGY, v. 10, NOV 12 2020. (19/14552-1, 19/14952-0, 17/26158-0, 20/04687-4, 19/06971-4, 19/11097-1, 19/12710-9, 20/07450-5, 18/15557-4, 19/14741-9)