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Action of melatonin in the intratumoral heterogeneity verified by the GLUT-1 and GLUT-3 glucose transporters in an animal model of breast Cancer

Grant number: 14/17957-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2015
Effective date (End): February 29, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Debora Aparecida Pires de Campos Zuccari
Grantee:Vinicius Rahal Mestrener
Home Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Breast cancer is the second most common cancer in women and one of the most commons in the world. Its rapid growth hinders blood perfusion in some regions, creating regions of hypoxia, which exerts a selective pressure on tumor subpopulations, selecting the fittest to survive in poorly oxygenated environment. The characteristics of each subpopulation and the adjustments undergone by them vary according to the region where they are, which characterizes the intratumoral heterogeneity. The differences include alterations in protein expression, such as the increased expression of glucose transporters GLUT-1 and GLUT-3 in hypoxia regions. This leads to increased glucose uptake contributing to an increase of anaerobic glycolysis instead of oxidative phosphorylation by tumor cells. Melatonin has been shown to be a potential treatment for breast cancer, and it is still needed a better understanding of its oncostatics mechanism. So, this study aims to assess melatonin influence on the intratumoral heterogeneity by identifying hypoxic regions with immunohistochemical using the GLUT-1 and GLUT-3 markers and subsequent comparison with the images obtained by positron emission tomography (PET) in a breast cancer animal model treated or not with melatonin.