Proceedings of Oncobiology Symposiums
Proceedings of the XV Oncobiology Symposium

INTRODUCTION AND OBJECTIVES: Obesity is a multifactorial disease characterized by adipose tissue (AT) meta-inflammation, presenting association with several types of cancer, including breast cancer, which is the most common type among women. The AT of obese individuals, in addition to secreting pro-inflammatory adipokines, releases a greater number of extracellular vesicles (EVs), which are small membrane vesicles capable of to transfer several molecules to target cells. It has been described that EVs are involved in the tumor microenvironment modulation, as in the epithelial-mesenchymal transition (EMT), which is defined by the loss of epithelial characteristics and the acquisition of the mesenchymal phenotype, triggering the increase in tumor cells malignancy. The aim of this study was to analyze the profile of AT secretome (conditioned medium (CM) and EVs) from lean and obese individuals and to evaluate whether this obese AT secretome is able to induce EMT in two human breast adenocarcinoma cells lineages: MCF-7 (non-invasive) and MDA-MB-231 (invasive). MATERIAL AND METHOD: Explants of subcutaneous and visceral AT were obtained from obese or lean patients (control group), who underwent to bariatric or plastic surgery, respectively. The adipokines profile released by AT were analyzed by Milliplex; Protein load in the EVs released by AT were analyzed by proteomics and Western blotting; Expression of EMT-related markers was assessed in breast tumor cells by Western blotting; Wound healing assay was performed to evaluate cell migration. RESULTS AND CONCLUSION: Our results have shown that, compared to lean AT, the CM from obese AT presented increased levels of pro-inflammatory adipokines (TNF-α, IL-6, TGF -β1, 2 and 3). Compared to lean AT, EVs released by obese AT presented higher content of proteins related to tumor progression, as S100A4, perlecan, galectin-1, and increased expression of TGF-β. The EVs released by obese AT induced a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal markers α-SMA in MCF-7 cells, and vimentin in MDA-MB-231 cells, compared to EVs released by lean AT. Reinforcing the pro-EMT effect of the obese AT-derived EVs on MCF-7 cells, we also observe increasing cell migration when compared to the CM and EVs released by lean AT. Together, our data indicate that EVs-derived obese AT present proteins with pro-tumor properties that appear to be capable of inducing EMT in breast tumor cells increasing their migratory capacity and thereby increasing their malignancy (CAAE 03769618.3.0000.5646).