Obesity, adipocytokines, and insulin resistance in breast cancer.
Obesity, adipocytokines, and insulin resistance in breast cancer.
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DOI：
10.1111/j.1467-789x.2004.00142.x
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发表时间：
2004-08-01
期刊：
影响因子：
--
通讯作者：
Stephenson, G D
中科院分区：
文献类型：
--
作者：
Rose, D P;Komninou, D;Stephenson, G D
脂肪细胞因子是生物活性多肽，其完全或基本上由脂肪细胞产生，并通过内分泌、旁分泌和自分泌机制起作用。大多数与肥胖、高胰岛素血症、2型糖尿病和慢性血管疾病有关;此外，六种脂肪细胞因子-血管内皮生长因子、肝细胞生长因子、瘦素、肿瘤坏死因子-α、肝素结合表皮生长因子样生长因子和白细胞介素-6-促进血管生成，而脂联素则具有抑制作用。肥胖和胰岛素抵抗都被认为是乳腺癌的危险因素，并与晚期疾病和预后不良有关。血管生成对于乳腺癌的发展和进展是必不可少的，因此肥胖相关的脂肪细胞因子产生的增加和脂联素的减少可能通过其血管生成相关的活性对乳腺癌的结果产生不利影响。还有实验证据表明，一些脂肪细胞因子可以直接作用于乳腺癌细胞，刺激其增殖和侵袭能力。因此，脂肪细胞因子可能提供了一种生物学机制，肥胖和胰岛素抵抗与乳腺癌风险和预后不良有因果关系。需要实验和临床研究来发展这一概念，特别是在预防和治疗选择有限的雌激素非依赖性乳腺癌中。
The adipocytokines are biologically active polypeptides that are produced either exclusively or substantially by the adipocytes, and act by endocrine, paracrine, and autocrine mechanisms. Most have been associated with obesity, hyperinsulinaemia, type 2 diabetes, and chronic vascular disease; in addition, six adipocytokines--vascular endothelial growth factor, hepatocyte growth factor, leptin, tumour necrosis factor-alpha, heparin-binding epidermal growth factor-like growth factor, and interleukin-6--promote angiogenesis while one, adiponectin, is inhibitory. Obesity and insulin resistance have both been identified as risk factors for breast cancer and are associated with late-stage disease and poor prognosis. Angiogenesis is essential for breast cancer development and progression, and so it is plausible that obesity-related increases in adipocytokine production and a reduction in adiponectin may adversely affect breast cancer outcome by their angiogenesis-related activities. There is also experimental evidence that some adipocytokines can act directly on breast cancer cells to stimulate their proliferation and invasive capacity. Thus, adipocytokines may provide a biological mechanism by which obesity and insulin resistance are causally associated with breast cancer risk and poor prognosis. Both experimental and clinical studies are needed to develop this concept, and particularly in oestrogen-independent breast cancers where preventive and therapeutic options are limited.