Development and characterization of malignant transformation models of prostate epithelial cells

• Grant number: 22/13217-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Maria Clara de Lobo e Mendonça
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Cancer is currently considered a highly prevalent malignant disease for being the second leading cause of death in the world, presenting a difficult early diagnosis and because its treatment, when available, is in many cases expensive and inaccessible. Among the cancers that stand out, we can mention prostate cancer, which is one of the most frequent in the male population. Oncogenesis, the process of development of cancer, happens in stages, with malignant transformation and tumor progression being two of them. In the first, essential in oncogenesis, cells acquire characteristics such as: differentiation; loss of function; uncontrolled proliferation; invasiveness and ability to undergo metastases, which allow them to carry out tumor progression, the next step in the process. The mechanisms of malignant transformation and its signs are diverse and not yet fully understood, unlike tumor progression, which is more studied. So, it is necessary to carry out in-depth studies on this transformation stage. The use of cellular models is an effective way of studying cancer, but in most existing models, malignant transformation has already occurred, since they are acquired after having gone through the initial stage of transformation. In these cases it is only possible to study cancer from the tumor progression and not from the malignant transformation. This project proposes the development of cellular models of malignant transformation of human prostate epithelial cells by the method of sequential cycles of adhesion and deadhesion, a technique that generates oxidative stress in cells, with consequent epigenetic changes, allowing a detailed analysis of malignant transformation, on each cycle. In addition to the development of models, tests will be performed to analyze the various characteristics of malignancy present in the transformed cells and their expression of specific molecules.