Modulation of Decorin expression in canine mammary neoplasms and its use as a prognostic biomarker and potential therapeutic target

• Grant number: 25/00245-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: February 28, 2029
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Ricardo de Francisco Strefezzi
• Grantee: Bethânia Almeida Gouveia
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mammary neoplasms are common in female dogs and this species is considered a model for comparative oncology research. Decorin (DCN) is an extracellular matrix protein involved in tumour suppression and has shown antilymphangiogenic activity in mouse models transplanted with mammary carcinoma. Traditional two-dimensional (2D) monolayer culture models are important for elucidating cellular mechanisms, but they fail to reproduce intrinsic characteristics of cellular architecture and interaction. Spheroids, three-dimensional in vitro cell culture models, reproduce the main characteristics of neoplasms in vivo. Considering the importance of DCN in tumour suppression and lymphangiogenesis in cancer progression, the aim of this study is to analyze the effects of DCN on aggressiveness and lymphangiogenesis in canine mammary carcinomas and to verify its potential prognostic value for the disease. For this purpose, the effects of DCN overexpression and silencing will be evaluated in 2D cultures and in spheroids of canine mammary carcinomas, as well as in co-culture with lymphatic endothelial cells. The expression of DCN, LYVE1 and PROX1 in canine mammary carcinomas will be evaluated by immunohistochemistry for comparison with histological type and grade, presence of distant and/or lymph node metastases and post-surgical survival. (AU)