Caracterização de corpúsculos e mediadores lipídicos em linhagens tumorais metastáticas e não metastáticas

Abstract

Lipid bodies (LB) are dynamic organelles that exert innumerable functionalities, especially the regulation of lipid metabolism, being present in normal cells and in cells associated with inflammatory processes. Breast cancer is a disease that presents high incidence in the population; where the increase of lipogenesis and cellular proliferative decontrol characterize the pathology. Several studies correlated to tumor progression with the quantification of lipid bodies, as well as the production of inflammatory mediators; Since in the advanced stages of the disease a high number of LB are observed at the tumor site, as well as the production of inflammatory mediators. Additionally, the knowledge of the role of mTOR signaling pathway has been used to suggest new therapies for cancer. Many studies aimed to elucidate the mechanisms that promote homeostasis, as well as the understanding of the progression of breast cancer, use two murine (4T1 and 67 NR), easily transplanted and tumorigenic lines for the right purposes. The present work consists of characterizing the production of inflammatory mediators and LB in two murine mammary tumor cells, one with invasive capacity (4T1) and the other non-metastatic (67NR), and in peritoneal macrophages treated with supernatant from 4T1 and 67NR cells. Concomitantly, the role of the mTOR pathway modulation of lipid metabolism was examined by treatment with rapamycin in the different cell types. For this study tumor cells were cultured at time intervals 24 and 48h in RPMI-1640 medium containing different concentrations of FBS (0 to 10%), pretreated or not with rapamycin. Our results demonstrated that the formation of LB in the two strains is directly proportional to the concentration of SFB used and the culture time. An increase in the production of leptin and TGF-β was observed, with respective decrease of adiponectin by the two strains studied. Additionally, we observed induction of LB and PGE2 synthesis in macrophages treated with tumor cell supernatants. After the treatment with rapamycin there was a inhibition of LB and increase of PGE2 when tumor cells and macrophages were pretreated with rapamycin. Concomitant with some studies, the participation of LB in tumor development is clear and its high quantification is related to a worse prognosis of cancer due to the production of inflammatory mediators. It should also be noted that the expressions of adiponectin and leptin can be considered as a marker of cancer evaluation, which high levels of leptin are seen in a worse prognosis in Breast Cancer.