The role of microglia activation in human astrocytoma

• Grant number: 13/07704-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2013
• Effective date (End): August 31, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Suely Kazue Nagahashi Marie
• Grantee: Thais Fernanda de Almeida Galatro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glioblastoma (GBM) is an aggressive form of brain tumor characterized by infiltration in the brain. GBM is generally resistant to chemotherapy and radiation. After surgical resection and treatment, virtually all GBM tumors recur within the first years after diagnosis, resulting in poor survival prognosis. In GBM, a small fraction of cells with neural stem cell (NSC)-like characteristics have been identified, termed as glioblastoma stem cells (GSC). GSCs have overlapping characteristics NSC, such as self-renewal and multi-lineage differentiation potential. GSCs are thought to be the primary drivers of tumor progression that are highly resistant to therapy. The microenvironment is recognized increasingly as an important factor in determining tumor progression. In GBM, the microenvironment contains astrocytes, neurons and most importantly, residing brain macrophages called microglia. These microglia cells are the immune cells of the central nervous system that react to disturbance in normal homeostasis by secreting pro-inflammatory cytokines. Aberrant activation of microglia is known to contribute to neuro-degeneration in diseases such as Parkinson's. In GBM, microglia cells have been highly studied in the context of immune responses, whereas the consequences of their inflammatory response on glioma cells proliferation, treatment resistance, migration and invasion have been highly overlooked. Several studies have demonstrated microglia activation in GBM patient samples. Moreover, GBM cells appear to induce pro-inflammatory activation of microglia. Here, we propose to study the inflammatory role of microglia in GBM disease progression. We hypothesize that differential activation of microglia and paracrine activity might affect the aggressiveness of GBM. This is a collaborative study between the University of Groningen and the University of São Paulo, which includes a technology transfer agreement and a PhD scholarship of two years supported by the University of Groningen. We are applying this project to FAPESP in order to obtain financial support for the two years of the PhD scholarship here in Brazil and the for the Brazilian samples analysis (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)

DE ALMEIDA GALATRO, T. F.; LERARIO, A.; MORETTI, I.; SOLA, P.; BERTOLDI, E. R.; FREITAS, V. G.; PEREIRA, T.; MARTINEZ, R. C.; MALDAUN, M. V.; EGGEN, B. J. L.; et al. Microglia exhibits proliferative and ECM modulating profiles in human gliomas. Glia, v. 65, p. 2-pg., 2017-06-01. (13/07704-3, 13/02162-8, 16/15652-1, 13/06315-3)

GALATRO, THAIS F.; HOLTMAN, INGE R.; LERARIO, ANTONIO M.; VAINCHTEIN, ILIA D.; BROUWER, NIESKE; SOLA, PAULA R.; VERAS, MARIANA M.; PEREIRA, TULIO F.; LEITE, RENATA E. P.; MOLLER, THOMAS; et al. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes. NATURE NEUROSCIENCE, v. 20, n. 8, p. 1162+, AUG 2017. (13/02162-8, 13/06315-3, 13/07704-3)

MORETTI, I.; GALATRO, T.; OBA-SHINJO, S.; MARIE, S.. Toll-like receptor expressions in human astrocytomas. Glia, v. 65, p. 2-pg., 2017-06-01. (13/07704-3, 13/02162-8, 13/06315-3)

Academic Publications

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

GALATRO, Thais Fernanda de Almeida. Human microglia expression profile and its alterations related to glioma. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.