Extracellular vesicles derived from neural precursors as modulators of the tumor microenvironment: glioblastoma organoids as a study model.

• Grant number: 22/03802-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): May 01, 2023
• Effective date (End): December 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Ester Alves Mota
• 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 (GBM) is a lethal brain tumor with a low life expectancy after diagnosis. It comprises several cell types that communicate through extracellular vesicles (EVs). Through miRNAs, proteins, lipids, and DNA, EVs can mediate cell-to-cell communication. Stem cells/neural precursors (NSCs) are responsible for brain neurogenesis and may be involved in the processes of emergence, recurrence and progression of GBM. Previous laboratory data characterized a repertoire of miRNAs obtained from NSC-derived EVs. Subsequent analyzes showed that some of these miRNAs are related to several types of cancer and have several long non-coding RNAs (lncRNAs) as targets, suggesting that these miRNAs may act in tumorigenesis-related pathways and in the regulation of gene expression in other cells. Therefore, the objective of this project is to evaluate the effect of EVs recovered from NSCs, obtained from the differentiation of hiPSCs (human induced pluripotency stem cells), on the biology of GBM organoids obtained from clinical samples. For this, NSC vesicles will be isolated, characterized, co-cultured with GBM organoids and later a proteomic analysis of treated and untreated GBM cells with NSC VEs will be performed. The evaluation of GBM protein expression may show functional evidence to identify biological processes related to the impact of neural precursor cells on tumor biology. Therefore, it will be possible to detect molecules for possible therapy candidates or biomarkers that are involved in the communication between these cell types.