Suppression of metastasis in breast cancer by the miRNA-200 family delivered by extracellular vesicles"

• Grant number: 23/14740-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2024
• End date: October 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Debora Aparecida Pires de Campos Zuccari
• Grantee: Caroline Patini de Rezende
• Host 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 (BC) metastasis is a complex process in which tumor cells spread to other organs, and is responsible for the majority of deaths caused by this disease. This phenomenon is one of the biggest concerns in the treatment of breast cancer, as it significantly increases its severity and hinders the effectiveness of available treatments. Despite numerous efforts dedicated to prevention, metastasis remains the main challenge faced by medical science in the context of BC. A better understanding of the molecular mechanisms involved in metastasis and the control of the expression of genes related to it can be an effective strategy for its prevention. In this context, the transfection of miRNAs into tumor cells with the aim of suppressing cancer-related proteins and transcription factors is considered a promising approach. ZEB1 is one of the transcription factors associated with metastasis, especially in the epithelial-mesenchymal transition, and can be inhibited by the miRNA-200 family. Although many studies have demonstrated the potential of miRNAs-200 in controlling ZEB1 and the subsequent expression of its downstream proteins, effective delivery of this miRNA through the bloodstream remains a significant challenge in the search for a viable injectable therapy. The objective of this study is to use extracellular vesicles (EVs) loaded with the miRNA-200 family, for direct delivery into BC cells in order to promote the suppression of metastasis. EVs will be obtained from adipose tissue mesenchymal stem cells and loaded with miRNA-200. Subsequently, we will investigate the impact of VEs/miR200 treatment, both with and without exposure to TGF- beta on MDA-MB-231, MCF7 e 4T1 cells, evaluating the levels of ZEB1 and other proteins associated with metastasis, as well as apoptosis and angiogenesis. Furthermore, an in vivo experiment will also be carried out to evaluate the control of metastasis in the main organs of female mice xenografted with BC after VEs/miRNA injection. Therefore, our study may represent a promising advance in the development of new effective anti-metastatic drugs for breast cancer patients.