Adipocytokines such as
leptin and
adiponectin have functions in metabolism as well as the development and progression of various types of
malignancies. However, little is known about their role in
bladder cancer. In this study, we investigated whether
leptin,
adiponectin, and their receptors have an impact on
bladder cancer outgrowth and the mechanisms involved. We performed immunohistochemistry for
leptin,
leptin receptor (Ob-R),
adiponectin, and
adiponectin receptors (AdipoR1, AdipoR2) in
bladder cancer tissue microarrays. Wound healing assay and western blot were then performed in human
bladder cancer lines. The positive rates (0 vs 1+/2+/3+) of Ob-R (P=0.004),
adiponectin (P<0.001), AdipoR1 (P=0.016), and AdipoR2 (P<0.001) expression were significantly higher in
bladder tumors than in benign urothelial tissues. Strong (3+)
leptin expression tended to be present more often in
tumors (10.2%; P=0.079) than in benign tissues (3.2%). Multivariate analysis revealed a lower risk of recurrence (hazard ratio [HR]=0.432; 95% confidence interval [CI]=0.198-0.942; P=0.034) in patients with an
adiponectin-positive non-muscle-invasive
tumor and a higher risk of progression (HR=5.148, 95% CI=1.190-22.273; P=0.028) in patients with a
leptin-positive muscle-invasive
tumor. Treatment of two
bladder cancer cell lines with a synthetic
adiponectin inhibited their migration and the expressions of phospho-NF-κB, NF-κB, snail, slug,
Y-box-binding protein 1, and COX-2, whereas
leptin showed reverse effects. Downregulation of
adiponectin expression and upregulation of
leptin expression were independent predictors for the recurrence of non-muscle-invasive
bladder tumors and progression of muscle-invasive
bladder tumors, respectively. In summary, synthetic
adiponectin might exhibit antitumor activity against
bladder cancer.