Obesity promotes melanoma tumor growth: Role of leptin

Abstract

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