The roles of nitric oxide (NO) and reactive oxygen species (ROS) in platelet aggregation induced by triple-negative human breast tumor cells

• Grant number: 22/09228-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2022
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Hugo Pequeno Monteiro
• Grantee: Isabelle Turco de Almeida
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15038-7 - Tumor development under the perspective of redox signaling: temporal modulation of the production of nitric oxide and reactive oxygen species, AP.TEM

Abstract

The World Health Organization (WHO) points to cancer as one of the leading causes of death in the world. The microenvironment of the tumor can be described as chronic inflammation, as a "wound" that does not heal. In this chronic inflammatory environment, inflammatory cytokines, reactive oxygen species (ROS), and nitric oxide (NO) are produced, which influence the processes of cell signaling and acting in epithelial-mesenchymal transitions - EMT and mesenchymal-epithelial- MET, favoring tumor dissemination. Studies show that individuals with solid tumors have abnormality in the activation of the coagulation system, which ends up resulting in thromboembolism, facilitating tumor dissemination through the secretion of proteins, bioactive lipids, and expression of surface molecules in platelets. These events act as facilitators of tumor dissemination. Among the different types of cancers, breast cancer, which involves solid tumors through ductal hyperproliferation, is the type of cancer that mostly affects women in Brazil. In breast cancer as well as in other types of cancer, metastasis to distant organs depends on the interaction between lymphatic and blood microenvironment and tumor cells. These interactions provide the establishment of new colonies of tumor cells in distant organs such as bones, lungs, liver, and brain. However, the processes involved in the interaction of platelets with breast tumor cells (participation of molecules in the recognition and activation of platelet aggregation, as well as the transport of these cells) have not been fully understood to date. Thus, studies that seek to understand the mechanisms involved in platelet aggregation, induced by tumor cells, are essential in the formulation of therapeutic strategies to combat and prevent an association between the progression of breast cancer and thromboembolism. This study aims to investigate the role of NO formation produced by the enzyme NO inducible synthase (NOS2) in cells of the human breast cancer lineage of the triple-negative subtype, MDA-MB-231, in the regulation of platelet aggregation stimulated by these cells.(AU)