Rose D P, Komninou D, Stephenson G D
Institute for Cancer Prevention, One Dana Road, Valhalla, NY 10595, USA.
Obes Rev. 2004 Aug;5(3):153-65. doi: 10.1111/j.1467-789X.2004.00142.x.
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.
脂肪细胞因子是一类生物活性多肽,它们要么仅由脂肪细胞产生,要么主要由脂肪细胞产生,并通过内分泌、旁分泌和自分泌机制发挥作用。大多数脂肪细胞因子都与肥胖、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。肥胖和胰岛素抵抗均已被确定为乳腺癌的危险因素,且与晚期疾病和不良预后相关。血管生成对于乳腺癌的发生和发展至关重要,因此,肥胖相关的脂肪细胞因子产生增加和脂联素减少可能通过其与血管生成相关的活动对乳腺癌的预后产生不利影响,这是有道理的。也有实验证据表明,一些脂肪细胞因子可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一种生物学机制,通过该机制肥胖和胰岛素抵抗与乳腺癌风险及不良预后存在因果关系。需要开展实验研究和临床研究来拓展这一概念,尤其是在雌激素非依赖性乳腺癌中,因为其预防和治疗选择有限。