ANNEXIN A1 EXPRESSION IN TRAMP MICE TUMOR PROGRESSION AND ITS MODULATION BY DOCOSAHEXAENOIC ACID

• Grant number: 22/07900-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2022
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Rejane Maira Góes
• Grantee: Lucas Pagliuca Martins
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Prostate cancer (PCa) is one of the leading causes of death in men by cancer-related cases. Inflammation and diet directly affect the risk of developing PCa. Several reports show that docosahexaenoic acid, an omega-3 fatty acid, displays an anti-tumor effect on PCa, however, more studies are needed to clarify its effects on tumor progression. Annexin A1 (ANXA1), an anti-inflammatory protein, is associated with the prognosis of different types of cancer, but its role in prostate cancer is still unclear. This study aims at evaluating the ANXA1 tissue expression on tumor progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP). Additionally, we will examine if a docosahexaenoic-enriched diet affects the ANXA1 expression and its effects on PCa progression in this mouse model regarding epithelial-mesenchymal transition. TRAMP mice will be divided into four experimental groups: animals fed with a standard diet and euthanized at 12 (C12) or 18 (C18) weeks old and animals fed with a docosahexaenoic acid-enriched diet at 8 weeks old and euthanized at 12 (T12) or 18 (T18) weeks old. The ventral prostate or tumors will be collected and processed for paraffin embedding. Tissue expression of ANXA1, E- and N-cadherin, and the Snail transcription factor will be assessed through immunohistochemistry, and ANXA1 expression through normal epithelial areas, low and high-grade intraepithelial neoplasia, carcinoma in situ and undifferentiated adenocarcinoma will be estimated based on densitometry analysis. Total ANXA1 content will be analyzed by Western blotting of ventral prostate samples. With this study, we intend to improve the knowledge of ANXA1 expression on PCa progression in the TRAMP model, as well as the effects of docosahexaenoic acid intake on tumor microenvironment, ANXA1 expression, and the disease progression.