Obesity promotes melanoma tumor growth: Role of leptin

Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1x106 B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R-/-), which have high leptin levels, obese leptin-deficient (ob-/-), pair fed lean ob-/-, and lean ob+/- mice. Mean body weights were 29.7±0.3 g (WT), 46.3±1.9 g (MC4R-/-), 63.7±0.9 g (ob-/-), 30.5±1.0 g (pair fed ob-/-), and 31.6±1.7 g (ob+/-). Tumors were much larger in the obese leptin deficient ob-/- (5.1±0.9 g) and obese MC4R-/- (5.1±0.7 g) than in lean WT (1.9±0.3 g) and ob+/- (2.8±0.7 g) mice. Prevention of obesity by pair feeding ob-/- mice dramatically reduced tumor weight (0.95±0.2 g) to a level that was significantly lower than in WT mice of the same weight. Tumor VEGF levels were the highest in the obese mouse tumors (p