Analysis of the effect of TGF-²1-induced epithelial-mesenchymal transition on cisplatin sensitivity in germ cell tumors

• Grant number: 18/18808-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Larissa Alessandra Bourdeth Pereira
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Germ cell tumors (GCTs) are benign or malignant neoplasms, divided into seminomatous and non-seminomatous, with different levels of differentiation, that can occur in gonadal or extragonadal sites. The GCTs treatment is based on histogenesis tumors, but it is known that the cisplatin treatment has a great relevance when patients' survival is observed. One of the mechanisms related to tumor progression, metastasis and drug resistance is the epithelial-mesenchymal transition (EMT). EMT is a process characterized by a shift from the cell's epithelial phenotype to a mesenchymal phenotype, giving it migration and invasion abilities. This transition can be induced by several factors and the main one is the transforming growth factor beta (TGF-²). However, the role of cisplatin in the EMT induced by TGF-²1 in GCTs has not been investigated. This way, the aim of this study is to evaluate the effect of TGF-²1-induced EMT on cisplatin sensitivity in GCTs. For the development of this study, the human embryonal carcinoma cell line (NTERA-2) will be treated in three different conditions: I) TGF-²; II) Cisplatin; III) TGF-² + Cisplatin. After the treatments, the expression of some EMT-related genes will be evaluated by real-time PCR and proteins will be analyzed by Western blot. Cellular migration ability will also be evaluated. Understanding the effect of EMT on cisplatin sensitivity will allow a better comprehension of this drug in the treatment of GCTs, as well as contribute to the development of novel therapeutic approaches.