Meta-inflammation Enhances Migration and Invasion of Prostate Cancer Cells via S100A4 Signaling 2267403

Abstract

Abstract Introduction Prostate cancer is one of the most commonly diagnosed cancers in American men and a leading cause of cancer-related death, largely due to incurable metastatic disease. Obesity has been linked to increase the risk of developing aggressive and fatal prostate cancer, in part through chronic low-grade inflammation, or meta-inflammation. Within the tumor microenvironment, macrophage-derived inflammatory mediators promote cancer progression. Tumor-associated macrophages are key drivers of this process. This study aimed to investigate the molecular and cellular mechanisms linking meta-inflammation to prostate cancer cell migration and invasion. Methods An in vitro co-culture model that mimics the macrophage-to-adipocyte ratio observed in obese adipose tissue was established using human adipocytes (from donors with BMI ≥30) and U937 macrophage-like cells. Three conditions were tested: unstimulated, acute inflammation (10 ng/mL LPS for 24 h), and chronic inflammation (adipocytes pretreated with 10 ng/mL LPS for 24 h followed by 24 h in basal media). This low-dose LPS protocol mimics the metabolic endotoxemia commonly seen in obesity. Conditioned media from each condition were used to stimulate DU145 human prostate cancer cells. Results Transwell migration, invasion, and wound-healing assays showed that DU145 cells treated with conditioned media from acute and chronic inflammatory co-cultures displayed significantly increased migration and invasion compared with controls. Western blotting and immunofluorescence revealed upregulated S100A4, a protein associated with inflammation and cancer progression. Conclusion These findings suggest that obesity-associated meta-inflammation enhances prostate cancer cell migration and invasion, shedding light on mechanisms through which chronic inflammatory signaling may promote metastatic progression. Funding Source n/a Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)