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Modulation of the neural phenotype of glioblastoma stem cells by extracellular miRNA from NSCs

Grant number: 19/11097-1
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2019
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Marilene Hohmuth Lopes
Grantee:Maria Isabel Melo Escobar
Home 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 Glioblatoma Multifome (GBM) is a highly aggressive and lethal type of tumor derived from glial cells. Its high recurrence rate can be attributed to its resistance to conventional treatments and diffuse growth pattern. Studies shows that the GBM is maintained by a sub-population of cells with stem cell like characteristics, denominated Glioblastoma Stem Cells (GSCs). GSCs share several phenotypical and functional aspects with Neural Stem Cells, due to the tendency of cancer to replicate ontogeny (Lathia et al., 2015). Those cells can give rise to highly proliferative cells and invasive cells, contributing to the survival of the tumor. Our group has described the role of the Protein Prion Cellular (PrPC) in the biology of the NSC and GSCs, 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. NSCs exhibit an inherent tropism to GBM (Aboody et al., 2000; Benedetti et al., 2000), reduce stem-like phenotypes, induce GSCs differentiation (Zhang et al., 2014) and suppress tumor growth in vivo (Staflin et al., 2009). Understanding the differentiation control of GSCs is important to convert these cells into a more mature state with reduced proliferative capacity. Extracellular vesicles (EVs) had been recognized as intercellular messengers implicated in the transfer of distinct molecules, including miRNA, to modify the phenotype of recipient cell. Thus, we interrogated the potential miRNA from NSCs-derived EVs targeting GSCs and stimulate their differentiation. The profiling of miRNAs from EVs during NSCs differentiation has been characterized in our previous Young Investigator Award (FAPESP#11/13906-2, data not shown). Interestingly, we found miRNA as a direct targeting of PrPC and also proteins related to neural cell fate (data not shown) in NSCs-derived EVs. EVs containing miRNA might represent an additional strategy to modulate phenotype acquisition in GSCs. Thus, the main goal of this work is to identify miRNA associated to neural commitment of GSCs. The differentiation of GSCs may be a relevant strategy to limit tumorigenic capacity by shifting the fate of cells to a mature state and consequently attenuates aggressiveness. (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)
IGLESIA, REBECA PIATNICZKA; DE LIMA FERNANDES, CAMILA FELIX; COELHO, BARBARA PARANHOS; PRADO, MARIANA BRANDAO; MELO ESCOBAR, MARIA ISABEL; DONA RODRIGUES ALMEIDA, GUSTAVO HENRIQUE; LOPES, MARILENE HOHMUTH. Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 22 NOV 2019. Web of Science Citations: 0.
DE LIMA FERNANDES, CAMILA FELIX; IGLESIA, REBECA PIATNICZKA; MELO-ESCOBAR, MARIA ISABEL; PRADO, MARIANA BRANDAO; LOPES, MARILENE HOHMUTH. Chaperones and Beyond as Key Players in Pluripotency Maintenance. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 7, AUG 2 2019. Web of Science Citations: 1.

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