Role of Annexin A1 in primary melanoma: in vivo and spheroid study

• Grant number: 24/10195-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Sarah Eloísa Esteves Conceição
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/11602-0 - Annexin A1 and neutrophils: mechanisms involved in gestation, Melanoma metastasis and Intestinal Ulcerative Disease, AP.R

Abstract

Melanoma is an aggressive skin cancer that originates from mutations in melanocytes. Although rare, it is the most lethal type of skin cancer. Genetic factors, such as mutations in the NRAS, NF1 and BRAF V600K genes, as well as a fair skin phenotype, are associated with the risk of developing melanoma. Survival depends on the stage at which the cancer is diagnosed and treatments range from surgical removal to immunotherapy.Annexin A1 (AnxA1) is a protein that binds to membrane phospholipids in the presence of calcium, performing multiple biological functions, including anti-inflammatory actions and tumor development. It binds to formylated receptors (FPRs), promoting cell proliferation and migration, fundamental processes in both tissue regeneration and tumor progression. Recent studies show that melanoma cells produce AnxA1 and express formylated receptors which, when activated, promote cell proliferation, migration and invasion. In addition, AnxA1 is expressed on immune cells in the tumor microenvironment, which may also be involved in melanoma progression.The aim of this project is to investigate the role of AnxA1 in the formation of primary melanoma and in cell organization for tumor formation using spheroids. To this end, B16F10 melanoma cells silenced or not for the AnxA1 expression gene will be used. These will be administered subcutaneously to C57B6 mice to develop the primary lesion or will be used to form spheroids in vitro. The tumor formed will be surgically extracted for histological analysis and the spheroids will be used for analysis of cell adhesion expressions. This experimental approach will allow us to evaluate the role of AnxA1 expressed by the melanoma cell in tumor development in vivo and in vitro, and will provide data to clarify the cellular mechanism of AnxA1 in melanoma. It will also provide technical and scientific training for undergraduate students in cell and molecular biology.