Study of secondary structures in astrocytomas: quantitative analysis of infiltrative growth and its correlation with ADAM23 gene expression in animal models

• Grant number: 17/13622-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2018
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Erico Tosoni Costa
• Grantee: Natália Cristina dos Santos
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated scholarship(s): 19/06305-4 - Three-dimensional morphometric analysis: quantifying the infiltrative growth of astrocytomas in animal model, BE.EP.IC

Abstract

Astrocytomas are aggressive tumors from the central nervous system (CNS) developing from astrocytes. The most common and fatal subtype is the Glioblastoma Multiforme (GBM, grade IV, WHO). High-grade astrocytomas (grades III and IV) exhibit a so-called "infiltrative growth" pattern of brain spreading, which emerges as a combination of uncontrolled cell proliferation and intense parenchymal invasion. High-grade astrocytomas are resistant to current therapeutic regimens. Our group has been focus on the role of the ADAM23 gene in astrocytoma cells. ADAM23 is a catalytically inactive member of the ADAM family (the family of disintegrins and metalloproteinase) that is frequently found silenced in different types of tumors. ADAM23 appears to be preferentially expressed in the central nervous system and has a crucial physiological role in neuronal differentiation and brain development. Despite this, little is known about the role of ADAM23 for CNS tumors. The scope of this project is to quantify the proliferative and invasive components of astrocytoma cells expressing different levels of ADAM23. Furthermore, we will also investigate the correlation between ADAM23 levels and the pattern of infiltrative growth in samples of human primary astrocytomas, as assessed by morphometric analyzes of their respective MRI images and by gene set enrichment analysis (GSEA). This project comes to be part of a larger project that is being developed in our laboratory (FAPESP # 2016 / 07463-4). (AU)