Department of Cell Biology and Centro Sanitario, University of Calabria, via Pietro Bucci, 87036 Arcavacata di Rende, Italy. sebastiano.ando@ unical.it
Nat Rev Endocrinol. 2011 Nov 15;8(5):263-75. doi: 10.1038/nrendo.2011.184.
Adipose-tissue-derived signaling molecules, including the adipokines, are emerging as key candidate molecules that link obesity with cancer. Peritumoral, stromal, adipose tissue and secreted adipokines, particularly leptin, have important roles in breast cancer biology. For example, leptin signaling contributes to the metabolic features associated with breast cancer malignancy, such as switching the cells' energy balance from mitochondrial β-oxidation to the aerobic glycolytic pathway. Leptin also shapes the tumor microenvironment, mainly through its ability to potentiate both migration of endothelial cells and angiogenesis, and to sustain the recruitment of macrophages and monocytes, which in turn secrete vascular endothelial growth factor and proinflammatory cytokines. This article presents an overview of current knowledge on the involvement of leptin in the pathogenesis and progression of breast cancer, highlighted by human, in vitro and animal studies. Data are presented on the functional crosstalk between leptin and estrogen signaling, which further contributes to promotion of breast carcinogenesis. Finally, future perspectives and clinical applications in which leptin and the leptin receptor are considered as potential therapeutic targets for breast cancer are reviewed.
脂肪组织衍生的信号分子，包括脂肪因子，正在成为将肥胖与癌症联系起来的关键候选分子。肿瘤周围、基质、脂肪组织和分泌的脂肪因子，特别是瘦素，在乳腺癌生物学中具有重要作用。例如，瘦素信号有助于与乳腺癌恶性相关的代谢特征，例如将细胞的能量平衡从线粒体β-氧化切换到有氧糖酵解途径。瘦素还塑造了肿瘤微环境，主要通过增强内皮细胞的迁移和血管生成的能力，并维持巨噬细胞和单核细胞的募集，而这些细胞反过来又分泌血管内皮生长因子和促炎细胞因子。本文概述了目前关于瘦素在乳腺癌发病机制和进展中的作用的知识，重点介绍了人类、体外和动物研究的数据。还介绍了瘦素和雌激素信号之间的功能串扰，这进一步促进了乳腺癌的发生。最后，回顾了将瘦素和瘦素受体视为乳腺癌潜在治疗靶点的未来展望和临床应用。
