Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production
Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production
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DOI：
10.1186/1756-9966-30-21
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发表时间：
2011-02-21
影响因子：
11.3
通讯作者：
Narimani, Manijeh
中科院分区：
文献类型：
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作者：
Amjadi, Fatemehsadat;Javanmard, Shaghaygh Haghjooy;Narimani, Manijeh
背景：流行病学研究表明，肥胖会增加几种癌症的风险，包括黑色素瘤。肥胖会增加瘦素的表达，瘦素是一种主要由脂肪细胞产生的多功能肽，可能会促进肿瘤的生长。最近的一些实验表明，肿瘤的生长需要内皮祖细胞(EPC)依赖的新血管的生成。本研究的目的是观察瘦素对黑色素瘤生长、循环内皮祖细胞数量和血浆一氧化氮代谢产物(NOx)水平的影响。第8天将小鼠随机分为4组(n=8)。两组均每日两次腹腔注射PBS或重组小鼠瘦素(1mUg/g初始体重)。两组均接受腹腔注射。连续3天注射抗瘦素受体抗体9F8或对照小鼠免疫球蛋白50微克/只。结果：Leptin组、PBS组、9F8组和Ig G组的肿瘤重量、内皮祖细胞数和NOx水平分别为(3.2±0.6，1.7+/-0.3，1.61+/-0.2，1.7+/-0.3g)，(222.66+/-36.5,133.33+/-171，23.33+/-18,132.66+/-27.26/ml)，和(22.47+/-5.5，12.30+/-1.5，6.26+/-0.84，15.75+/-6.3 Mol/L)。瘦素组肿瘤重量和大小、循环内皮细胞数量和血浆NOx水平均显著高于9F8组和两个对照组(p<；0.05)。与对照组相比，9f8处理组小鼠血浆中NOx浓度显著降低(p<；0.05)。结论：我们的观察结果表明，瘦素可能通过增加NO的产生和循环中的EPC数量，从而促进血管生成而导致黑色素瘤的生长。
Background: Epidemiological 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).Methods: 2 x 10(6) 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 mu g/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 mu g/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed.Results: The 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 mu mol/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).Conclusions: In conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.