The effects of exercise training on the expression of myokines in extracellular vesicules in breast cancer: a translational approach

• Grant number: 22/00405-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 01, 2022
• End date: June 30, 2023
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Carlos Ugrinowitsch
• Grantee: Guilherme Defante Telles
• Supervisor: Mark A. Febbraio
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Monash University, Australia
• Associated to the scholarship: 20/06262-0 - Effects of combined training in the c-miRNAs expression in women with Breast Cancer, BP.DR

Abstract

Emerging evidence has highlighted the potential of exercise-induced crosstalk between skeletal muscle and cancer cells as one of the mechanisms controlling breast cancer progression. This intercellular communication seems to be mediated by a group of skeletal muscle molecules released in the bloodstream known as myokines, mainly inserted in extracellular vesicules (EVs). Among the myokines, exercise-induced Decorin and circulating microRNAs (c-miRNAs) are deemed to mediate the antitumoral effects produced by exercise training. However, there are still many open questions regarding the molecular basis of the exercise-induced protective effects on breast cancer through myokines in EVs. Therefore, the first aim of the present internship project is to investigate the role Decorin plays in the protective effects of exercise on tumour development and metastasis. To test this, we propose an experimental design combining the administration of Decorin into female SCID mice inoculated with MDA-MB-231HM human breast cancer cells and in vivo bioluminescent imaging. Our second aim is to test if miRNAs are: a) important cargo in EVs that are transported from contracting skeletal muscle to other organs and tissues in the body to perform important physiological roles and b) one mechanism by which exercise can provide protection against breast cancer progression in a mouse model of breast cancer. To test these, we propose an experimental design combining miRNA-sequencing analysis of different tissues of mice (breast cancer model) injected with purified EVs from muscle specific Dicer KO (MDicerKO) or control (WT) mice (exercised and sedentary condition). Therefore, considering all the proposed experiments, the internship in Professor Febbraio's lab will allow to robustly test the hypothesis of the present PhD project with a translational approach (Animal study in Australia and Human study in Brazil). (AU)