Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production

Abstract

BackgroundEpidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Obesity increases the expression of leptin, a multifunctional peptide produced predominantly by adipocytes which may promote tumor growth. Several recently experiments have suggested that the tumors growth is in need of endothelial progenitor cell (EPC) dependent generation of new blood vessels.Our objectives in the present study were to examine the effects of leptin on melanoma growth, circulating EPCs number and plasma levels of nitric oxide metabolites (NOx).Methods2 × 106 B16F10 melanoma cells were injected to thirty two C57BL6 mice subcutaneously. The mice were randomly divided into 4 groups (n = 8) in 8th day. Two groups were received twice daily intraperitoneal(i.p) injections of either PBS or recombinant murine leptin (1 μg/g initial body weight). Two groups were received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed.ResultsThe tumor weight, EPC numbers and NOx level in leptin, PBS, 9F8, and IgG group were (3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2,1.7 ± 0.3 g), (222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26/ml of blood), and (22.47 ± 5.5, 12.30 ± 1.5, 6.26 ± 0.84, 15.75 ± 6.3 μmol/L) respectively. Tumors weight and size, circulating EPC numbers and plasma levels of NOx were significantly more in the leptin than 9f8 and both control groups (p < 0.05). The plasma concentration of NOx significantly decreased in 9f8 treated mice compare to control group (p < 0.05).ConclusionsIn conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.

Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth

“…In addition, it is plausible that lipid lowering agents may have a role in cancer prevention and/or supplemental treatment approaches to reduce cancer progression and/or improve clinical outcome in both the BRAF V600E-positive pre-malignancy and cancer settings. Obesity has been associated with an increased risk of malignant melanoma, which is approximately twice that in non-obese individuals, and worsens prognosis of malignant melanoma in diverse epidemiological and clinical studies (Amjadi et al, 2011; Antoniadis et al, 2011; Brandon et al, 2009; Chen et al, 2013; Dennis et al, 2008; Kirkpatrick et al, 1994; Oh et al, 2005; Pandey et al, 2012; Sergentanis et al, 2013; Shors et al, 2001). A recent study also links fat mass and obesity-associated (FTO), a gene associated with obesity and overeating, with an increased risk of malignant melanoma (Iles et al, 2013).…”

Molecular Pathways: Adiponectin and Leptin Signaling in Cancer

“…Recombinant leptin treatment increased MDA-MB-231 breast tumor xenograft growth 22 as well as melanoma 78 . In an animal study, female mice in the MMTV-TGF-alpha breast cancer model fail to develop tumors when crossed with leptin deficient mice 46 .…”

Leptin’s Pro-Angiogenic Signature in Breast Cancer

“…In contrast, a more recent study used the same mouse melanoma cell line implanted into C57BL/6J mice, showed a significant increase of tumor growth (188%) after exogenous leptin supply. Furthermore, it was suggested that leptin might cause melanoma growth through increased NO production and circulating endothelial progenitor cell (EPC) numbers and consequently induced tumor angiogenesis [96]. …”