Metabolic reprogramming of normal human keratinocytes by melanoma extracellular vesicles

• Grant number: 22/16821-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Sophia Nora Baptista
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Melanomas are extremely aggressive tumors that originate from mutations in melanocytes. The high metastatic potential of melanomas is the main obstacle for treatment efficacy. Recently, several studies highlighted the relevant role played by the tumor microenvironment in several processes associated with tumor development and progression. Among the components of the tumor microenvironment, keratinocytes and small extracellular vesicles (sEVs) are closely related to the evolution of melanomas. Recent studies suggest the involvement of these vesicles in the modulation of metabolic pathways of cells from the tumor microenvironment and in the reprogramming of target cells, in a process known as tumor education. In parallel, evidence points to the presence of several alterations in mitochondrial and glucose metabolism in tumors, the Warburg effect being the best known example. Also, new research demonstrates the participation of metalloproteins (MMPs) and their inhibitors (TIMPs) in the development of neoplastic processes. Thus, in the present project, we propose to study the role of sEVs derived from melanoma cells (Skmel-28 and Skmel-29 and Skmel-29 resistant) in the metabolic reprogramming of keratinocytes, focusing on alterations in mitochondrial, glucose and in the action of metalloproteins. The understanding of the biochemical pathways involved in the education of keratinocytes by vesicles may provide subsidies for the establishment of rational strategies for the treatment of melanoma.