Heparins and heparinoids: potencial antiinflammatory, antiangiogenic an antitumor molecules

• Grant number: 24/20700-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2025
• End date: December 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Helena Bonciani Nader
• Grantee: Bianca Alves de Sousa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 23/07464-4 - Glycosaminoglycans and the cross-talk cell and extracellular matrix: a translational approach, AP.TEM

Abstract

Cancer is one of the leading causes of mortality worldwide, responsible for millions of deaths annually. The process of tumorigenesis involves complex cellular and molecular changes, including interactions with the extracellular matrix (ECM), which plays a fundamental role in tumor progression. Components of the ECM, such as glycosaminoglycans (GAGs), are subjects of study, with heparin being one of the most relevant. Besides its well-known anticoagulant function, heparin also exhibits anti-inflammatory and antitumor activities, and its chemically modified forms have been investigated as potential therapeutic agents in oncology. Therefore, this project aims to evaluate the antitumor and anti-inflammatory activities of chemically modified heparins, both in vitro and in vivo. The tumor cell lines to be studied include colorectal cancer cells (HT-29), breast adenocarcinoma (MDA-MB-231), and murine melanoma (B16-F10). In in vivo studies, a BALB/c mouse model will be used to assess the antimetastatic effects of modified heparins in breast cancer. This will involve evaluating cytotoxicity, cell proliferation, migration, and influence on endothelial tube formation, as well as analyzing cellular signaling pathways and induction of apoptosis. In vivo studies will include tumor induction in mice, monitoring tumor growth and metastasis via bioluminescence, and histological analysis of affected organs.