Role of PrPC and STI1/HOP in human glioblastoma stem cells biology in vivo.

Author(s)

Rebeca Piatniczka Iglesia

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2017-04-10

Examining board members

Marilene Hohmuth Lopes; Niels Olsen Saraiva Câmara; Alison Colquhoun; Erico Tosoni Costa; Silvya Stuchi Maria Engler

• Advisor: Marilene Hohmuth Lopes; Tiago Góss dos Santos

Abstract

GBM is the most aggressive type of glioma, presenting undifferentiated cells (GSCs), responsible for proliferation, invasion and tumor recurrence. We evaluated the role of the PrPC and its ligand HOP in the proliferation and self-renewal of GSCs. We cultured human GBM lineages in neurospheres and generated knockdown populations for PrPC and HOP. We observed co-localization of PrPC and CD133 on the surface and their co-stimulated copper internalization, suggesting PrPC-mediated recruitment of CD133. PrPC silencing reduces the expression of stem cell markers and self-renewal, decreases adhesion proteins expression, and affects cell migration. HOP silencing reduces proliferation, recovered with HOP treatment in PrPC+ cells. The tumorigenic and proliferative capacity of neurospheres PrPC and/or HOP knockdown in vivo is decreased. Finally, a HOP peptide which blocks PrPC-HOP interaction inhibits proliferation and self-renewal in PrPC+ cells, indicating PrPC-HOP complex potential as a target for therapies against GBM. (AU)

• FAPESP's process: 13/19860-0 - Study of PrPc and STI1 interaction in human glioblastoma stem cells in vivo
• Grantee: Rebeca Piatniczka Iglesia
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)