Associate Professor SUNY Old Westbury, New York, United States
Disclosure(s):
Maria Z. Cabail, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
