1760-P: The Secretome of Visceral Adipose Cells from Obese Subjects Promotes Epithelial–Mesenchymal Transition of Human Breast Cancer Cell Line MCF7

Introduction and Objective: The mechanisms linking obesity to heightened cancer risk and increased distal metastasis remain inadequately explored. This study investigates the potential harmful role of the secretome derived from abdominal visceral (AV) mature adipocytes of obese (Ob) subjects in promoting the epithelial-mesenchymal transition (EMT) in the non-advanced human breast cancer cell line MCF7. Methods: AV mature adipocytes were isolated from 29 non-obese (n-Ob) and 30 obese (Ob) subjects. The secretome was collected after 96 hours of cell culture. MCF7 cells were exposed to the secretome from Ob and n-Ob subjects at different time points. Results: The secretome of AV adipose cells from Ob subjects exhibited a distinct pattern of pro-inflammatory and anti-inflammatory cytokines. Levels of RANTES, MIP1B, and IFN-γ were significantly elevated in Ob compared to n-Ob subjects, and were directly correlated with BMI (p <0.05). Furthermore, levels of pro-inflammatory cytokines RANTES and IFN-γ were significantly higher in both the secretome and serum of Ob vs n-Ob subjects (p <0.05). Exposure of MCF7 cells to the secretome from Ob, but not from n-Ob subjects, resulted in increased phosphorylation of c-Jun and STAT3 (p <0.05), as well as impairment of actin filaments, evidenced by an increase in filopodia structures. The secretome from Ob subjects significantly upregulated protein expression of EMT markers, such as Vimentin and COX2 (p <0.05), while reducing the epithelial marker E-Cadherin (p <0.05). Conclusion: In human obesity, the secretome of AV mature adipocytes is enriched in pro-inflammatory cytokines that activate stress kinases, increase the expression of EMT markers, and induce cytoskeletal rearrangements, including the formation of filopodia structures. These changes are known to facilitate cell migration and tumor dissemination, highlighting a mechanistic link between obesity and cancer risk and progression. Disclosure G. Palma: None. C. Caccioppoli: None. R. Doria: None. V. Zanghi Buffi: None. I. Calderoni: None. V. Genchi: None. A. Braun: None. A. Cignarelli: None. A. Natalicchio: Speaker's Bureau; AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi. L. Laviola: Speaker's Bureau; A. Menarini Diagnostics, Abbott, AlfaSigma, Ascensia Diabetes Care, AstraZeneca. Advisory Panel; Boehringer-Ingelheim, Eli Lilly and Company. Speaker's Bureau; Boehringer-Ingelheim, Eli Lilly and Company. Research Support; Medtronic. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. A. Pezzolla: None. F. Giorgino: Advisory Panel; Abbott. Consultant; Amgen Inc. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Biomea Fusion, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly and Company. Research Support; Eli Lilly and Company. Board Member; European Association for the Study of Diabetes. Consultant; Medtronic. Advisory Panel; Mundipharma, Novo Nordisk, Roche Diabetes Care. Research Support; Roche Diabetes Care. Advisory Panel; Sanofi. S. Perrini: None. Funding PNRR-MAD-2022-12375797 Type 2 diabetes, Obesity, and Chronic Stress as predisposing Network for Tumorigenesis