Study of PrPc and STI1 interaction in human glioblastoma stem cells in vivo

• Grant number: 13/19860-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): January 01, 2014
• Effective date (End): March 31, 2017
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Rebeca Piatniczka Iglesia
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glioblastomas (GBM) are highly lethal brain tumors, which contains a subpopulation of Glioblastoma Stem Cells (GSC) capable of promoting tumor angiogenesis, invasion and radiotherapy and chemotherapy resistance, contributing to the failure to treat these cancers. Studies show that the interaction of two proteins, the cellular prion protein (PrPC) and stress inducible protein 1 (STI1), promote proliferation of GBM and recent data from our group indicate that the blocking of the PrPC-STI1 interaction may have therapeutic potential. Both PrPC and STI1 are highly expressed in the CNS. Their interaction modulates processes involved in neural plasticity and plays an important role in the biology of Neural Stem Cells (NSC), promoting proliferation and self-renewal. Based on these data, this study aims to evaluate the role of PrPC-STI1 interaction in the biology of GSC. Our data suggest that the PrPC-STI1 interaction is involved in GSC self-renewal and proliferation, in which the addition of STI1 in culture medium in clonal density and BrdU incorporation assays seems to promote dose-dependent proliferation in GBM human strain. However, PrPC-nonexpressing cells didn't show response to treatment with STI1, suggesting that the proliferative effect is dependent on interaction with PrPC. The elucidation of mechanisms controlling GSC proliferation is necessary to identify relevant targets for therapeutic intervention, increasing the effectiveness of treatment through the targeting of GSC, decreasing tumor invasion, proliferation, and even the recurrence of this tumor. (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)

CRUZ, LILIAN; ROMERO, JENNY A. A.; IGLESIA, REBECA P.; LOPES, MARILENE H.. Extracellular Vesicles: Decoding a New Language for Cellular Communication in Early Embryonic Development. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 6, AUG 28 2018. (17/20271-0, 14/17385-5, 13/19860-0, 11/13906-2, 13/22078-1)

IGLESIA, REBECA PIATNICZKA; PRADO, MARIANA BRANDAO; CRUZ, LILIAN; MARTINS, VILMA REGINA; SANTOS, TIAGO GOSS; LOPES, MARILENE HOHMUTH. Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells. STEM CELL RESEARCH & THERAPY, v. 8, APR 17 2017. (13/19860-0, 15/04122-9, 11/13906-2, 09/14027-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

IGLESIA, Rebeca Piatniczka. Role of PrPC and STI1/HOP in human glioblastoma stem cells biology in vivo.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.