Cellular Plasticity and SNAIL Expression in Germ Cell Tumors: Investigating Cisplatin Resistance Processes in 3D Models

• Grant number: 25/05564-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Maria Alice Brangion Silva
• Host Institution: Hospital do Câncer de Barretos. Barretos , SP, Brazil

Abstract

Childhood cancer is one of the leading causes of disease-related mortality, with germ cell tumors (GCTs) accounting for approximately 3% of pediatric neoplasms. Cisplatin is the standard chemotherapeutic agent used to treat GCTs; however, 15% to 20% of patients exhibit resistance to this compound. To overcome this challenge, three-dimensional (3D) culture models are used to investigate the molecular mechanisms associated with cisplatin resistance. One of the processes linked to resistance is the epithelial-mesenchymal transition (EMT), in which the transcription factor SNAIL plays a central role. Therefore, this study aims to evaluate cellular plasticity and the expression of the transcription factor SNAIL in GCTs, with an emphasis on the mechanisms of cisplatin resistance, using 3D models. For this purpose, 3D culture models will be established using parental and cisplatin-resistant GCT cell lines. Subsequently, the gene and protein expression of EMT markers, as well as migration and invasion capacity, will be assessed. Furthermore, SNAIL expression will be evaluated by immunohistochemistry in pediatric patients with GCTs and correlated with clinicopathological data. Statistical analyses will be performed using IBM SPSS 20.0 for Windows. Understanding EMT in cisplatin resistance in 3D models will provide deeper insights into the molecular mechanisms involved in GCTs. Additionally, this study aims to contribute to new knowledge and the development of novel therapeutic approaches.