Analysis of the role of TGF-² in drug resistance in germ cell tumors (GCTs) through regulating stem cell, apoptosis and epithelial-mesenchymal transition (EMT)

• Grant number: 18/13026-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2018
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Letícia Maria Barbosa Tufi
• Host Institution: Hospital do Câncer de Barretos. Barretos , SP, Brazil

Abstract

Germ cell tumors (GCTs) is a disease that affects around 3,3% of childhood cancers. The treatment of GCT is according to histogenesis presented by the tumor, but it is known that the treatment with cisplatin has a great relevance when observed the survival of the patients. However, some patients have resistance by this drug. A mechanism related to the development of cancer, metastasis and drug resistance is the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their characteristics and acquire mesenchymal cell phenotype with invasive and migratory capacity. This transition can be induced by several factors, which the main one is the transforming growth factor beta (TGF-²). Activation of EMT by TGF-² is also associated with the properties of cancer stem cells (CSCs) influencing the sensitivity of tumors to chemotherapeutic drugs. Therefore, this study aims to evaluate the role of TGF-² in germ cell tumors resistant to cisplatin treatment through regulating of EMT, CSCs and apoptosis. For the development of this proposal, cisplatin resistant GCT cell line will be used and TGF-² expression levels, EMT markers, apoptosis and stemness will be analyzed by real-time PCR, Western blot and flow cytometry. In addition, the migration and invasion cell capacity will also be evaluated. Understanding the role of TGF-² in resistance to cisplatin will allow a better compression of the molecular mechanisms involved in the treatment of GCTs and will contribute to the development of new therapeutic strategies.