Toll Like Receptor 4 role in glioblastoma cell lineages

• Grant number: 16/14695-9
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2017
• Effective date (End): February 28, 2019
• Field of knowledge: Health Sciences - Medicine
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Suely Kazue Nagahashi Marie
• Grantee: Isabele Fattori Moretti
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Toll like receptor 4 (TLR4) has a significant role in innate immunity. Right after activation, TLR4 signals through MyD88 pathway, producing a pro-inflammatory response and cell proliferation. This signal pathway induces NF-kB translocation to the nucleus and cytokine production. TLR4 is also internalized to the endosome and signals through TRIF, producing an anti-inflammatory response and apoptosis signaling. TLR4 expression was observed in Glioblastoma tumor cells in our laboratory. In others types of tumor, TLR4 stimulation has been reported to promote cell proliferation and survival. The main goal of this project is to verify the role of TLR4 in GBM tumor cell lines, as a proliferative or an apoptotic effector, by cell proliferation and cell survival assays. And, to analyze the involvement of NF-kB involvement and the product targets derived by TLR4 activation by qPCR. The research significance is to comprehend TLR4 activation dynamics that will lead to either proliferation and/or apoptosis, and contribute with new therapeutic strategies. This subject is included in the collaborative research with Dr Bart J. L. Eggen, from University of Groningen. The TLR4 study will be extended as a next step to its expression and its role in the microglia, the most abundant non-neoplastic cell in the tumor microenvironment in gliomas, where the interaction between these two cell compartments has been described to modulate tumor progression. (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)

MORETTI, ISABELE FATTORI; FRANCO, DAIANE GIL; DE ALMEIDA GALATRO, THAIS FERNANDA; NAGAHASHI MARIE, SUELY KAZUE. Plasmatic membrane toll-like receptor expressions in human astrocytomas. PLoS One, v. 13, n. 6, JUN 18 2018. (13/02162-8, 16/14695-9, 13/06315-3)

MORETTI, ISABELE F.; LERARIO, ANTONIO M.; TROMBETTA-LIMA, MARINA; SOLA, PAULA R.; SOARES, ROSELI DA SILVA; OBA-SHINJO, SUELI M.; MARIE, SUELY K. N.. Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. SCIENTIFIC REPORTS, v. 11, n. 1, JAN 14 2021. (13/02162-8, 16/14695-9, 15/26328-8, 04/12133-6)

TROMBETTA-LIMA, MARINA; ROSA-FERNANDES, LIVIA; ANGELI, CLAUDIA B.; MORETTI, ISABELE F.; FRANCO, YOLLANDA M.; MOUSESSIAN, ADALIANA S.; WAKAMATSU, ALDA; LERARIO, ANTONIO M.; OBA-SHINJO, SUELI M.; PASQUALUCCI, CARLOS A.; et al. Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma. JOURNAL OF PROTEOME RESEARCH, v. 20, n. 10, p. 4693-4707, OCT 1 2021. (14/06863-3, 16/14695-9, 15/26328-8)

Academic Publications

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

MORETTI, Isabele Fattori. Toll-like receptor 4 among the plasmatic membrane Toll like receptors plays a role in astrocytoma malignancy. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.