MAZO TAMARA MAGALI
Congresos y reuniones científicas
Título:
Extracellular vesicles from dietary compoundstimulated cancer associated fibroblasts trigger cell proliferation on breast cancer cells
Autor/es:
ERICA SOLLA; ROLDAN FRANCO; MAZO TAMARA; FERRERO VICTORIA; MARÍA EUGENIA PASQUALINI; AMADO QUINTAR
Reunión:
Workshop; II Workshop Extracellular vesicles in Biomedicine: Bringing EV to the clinic; 2023
Institución organizadora:
Centro de Investigación e Innovación Biomédica, UANDES/IMPACT
Resumen:
Dietary patterns provided by carbohydrates- and saturated fatty acid-rich food (CAP and FAP), representedmainly by fructose (F) and palmitic acid (PA) respectively, is positively associated with the risk of breast cancer,with the cellular mechanisms being far to be fully elucidated. We aimed to evaluate the dietary effects on themicroenvironment interactions between cancer-associated fibroblasts (CAFs) and tumoral cells, mediated byextracellular vesicles (EVs). Balb/c mice fed on CAP, FAP or CAP+FAP were s.c. implanted with LM3 mammarytumor cells. CAP+FAP tumors grew faster and with bigger volumes (p<0.05); by electron microscopy (TEM), ahigher frequency of CAFs, collagen and ultrastructural signs of increased secretion of EVs were seen. For invitro studies, the mammary CAFs cell line F88 was cultured and stimulated with F40mM, AP250uM, F+PAcombinations or their vehicles. Supernatants were collected and EVs isolated by sequential ultracentrifugation,characterized by TEM, and labeled with CD63. F+PA increases the frequency of 20-30 nm-sized EVs (p<0.05).Then, MCF7 cells were stimulated with conditioned media or with EVs derived from F-, AP-, and F+PA-treatedF88 cells, resulting in increased cell proliferation after EVs or conditioned media from F+PA, determined bybromodeoxyuridine and cell count (p<0.05). EVs from F+AP-treated F88 cells also decrease apoptosis, asmeasured by annexin V FACS in MCF7 and MDA-MB-231 cells. This pro-tumoral action of EVs was inhibitedby pre-incubating MCF7 with genistein, suggesting uptake in a clathrin-independent manner. These resultsindicate a pathogenic effect of dietary patterns rich in F and PA, via the release of pro-proliferative EVs by CAFsin breast cancer microenvironmen