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 1 × 106 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 deficientob−/− (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 < 0.05), regardless of the host leptin levels. Except for the lean ob+/−, MC4R−/− and ob−/− melanomas had the highest VEGF receptor 1 and VEGF receptor 2 protein expression (p < 0.01 and p < 0.05), respectively. These results indicate that obesity markedly increases melanoma tumor growth rate by mechanisms that may involve upregulation of VEGF pathways. although tumor growth does not require host leptin, melanoma tumor growth may be accelerated by leptin.

Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice

“…We hypothesize that ovariectomy (OVX) plus a high-fat diet with the inoculation of E0771 (mouse ER + breast cancer) cells in female wild-type >60 week old mechanisms that involve the upregulation of VEGF pathways. 15 The present study determines the following: (1) whether postmenopausal obesity increases VEGF expression, tumor angiogenesis and breast tumor growth in mice; (2) whether increased visceral fat size is correlated to increased breast tumor size; and (3) whether there is a difference in VEGF release from visceral fat compared to subcutaneous fat.…”

Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

“…Many factors may contribute to the effects of obesity on melanoma growth. Studies showed that adipocytes released IL-6 (15) and leptin (20) to promote melanoma growth and invasion. Understanding the roles of adipocytes in promoting melanoma growth may suggest an alternate and a direct therapeutic strategy to combat malignant melanoma.…”

“…Cells-Studies have demonstrated that obesity promotes melanoma tumor growth (19,20); therefore, we established a DIO mouse model for the study. We fed 5-week old male mice (C57BL/6) a high fat diet (Research Diets) and fed control mice a comparable control diet (Research Diets).…”

Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker

“…The risk for developing MM was found to be positively associated with serum levels of leptin and inversely with healthy lifestyle factors (6). Melanoma tumor growth may be accelerated by leptin (7).…”