O efeito de vesículas extracelulares do tecido adiposo obeso em células de câncer de mama

Abstract

Obesity can promote the dysregulated secretion of adipokines and pro-inflammatory responses in adipose tissue (AT), leading to metabolic dysfunction. Chronic low-grade inflammation installed in obesity may play a role in the pathogenesis of different diseases, including breast cancer. Among the mechanisms of cell-cell communication is the secretion of extracellular vesicles (EVs), which can alter the behavior of tumor/stromal cells and create a favorable niche for tumor progression. Therefore, the objective of this work was to evaluate the effect of EVs from adipose tissue on the behavior of breast cancer cells. Adipose tissue samples were collected from obese and eutrophic individuals according to BMI. Through sequential ultracentrifugation we isolated the VEs from these samples. These particles were characterized through analysis of diameter, protein markers, and internalization by tumor cells. Treatment with 5µg/mL of EVs from obese AT did not change the cell viability of MDA-MB-231 and MCF-7 cells, but reduced cell growth and the ability to form colonies of the MCF7 lineage. On the other hand, colony formation of MDA-MB-231 cells increased. In addition, these EVs increased the cell migration of both strains. EVs from the obese AT, but not from the control AT, increased TGF-β secretion from MDA-MB-231 cells and IL-1α from MCF-7 cells. In a high-fat diet-induced obesity model, EVs from the AT of obese mice impaired cell growth and promoted the migration of murine breast cancer 4T1 cells, when compared to untreated cells or treated with EVs from control animals. We did not observe differences in the secretion and expression of inflammatory markers from treated or untreated cells. These results suggest that the effect of EVs from obese adipose tissue depends on the cell type, but in accordance, they indicate an increase in the migration capacity of breast cancer cells. Additional studies are needed to identify possible agents and mechanisms of action in which these extracellular vesicles alter cellular behavior and their consequences for breast cancer progression.