ANTITUMORAL MECHANISMS OF EXERCISE-INDUCED EXTRACELLULAR VESICLES IN BREAST CANCER: POTENTIAL ROLE OF miRNAS FROM THE ADIPOSE TISSUE

• Grant number: 24/09705-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2025
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Guilherme Defante Telles
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

Breast cancer remains a critical global health concern. Exercise training is emerging as a non-pharmacological strategy to combat breast cancer. However, the mechanisms underlying its antitumoral effects are not fully understood. It has been suggested that exercise training can directly control tumor progression through intercellular communication mediated by extracellular vesicles (EVs) released transiently after repeated exercise bouts. It has been hypothesized that exercise-induced EVs might transfer their cargo to breast cancer cells, modulate key cellular processes, and consequently control cancer progression. Previous research has demonstrated the importance of EV-associated microRNAs (miRNAs) in mediating the antitumoral effects produced by exercise training. Our preliminary data indicate that EVs derived from acutely exercised mice (EEVs) significantly reduce breast cancer cell proliferation and viability in vitro. miRNA sequencing has revealed the upregulation of tumor suppressor miRNAs in EEVs. Notably, these miRNAs are also enriched in adipose tissue (AT), identified as a major source of EV-associated miRNAs. Additionally, preliminary findings from our ongoing clinical trial show that physical training might reduce Ki67 expression in breast tumors of patients before treatment, suggesting that EV-associated miRNAs from the AT may play a role in the antitumoral effects of exercise. However, the underlying molecular mechanisms of this response have not been fully elucidated. This project aims to mechanistically test the role of miRNAs contained in EEVs in the context of exercise training in breast cancer. Our central hypothesis is that miRNAs produced by the AT in response to exercise are encapsulated into extracellular vesicles, secreted into circulation, and reach the tumor to act as key mediators of the antitumoral effects induced by exercise training in breast cancer.