肥胖相关脂肪组织微环境在癌症发生发展中的作用。
The obese adipose tissue microenvironment in cancer development and progression.
机构信息
Goodman Cancer Research Centre, Department of Physiology, McGill University, Montreal, Quebec, Canada.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
出版信息
Nat Rev Endocrinol. 2019 Mar;15(3):139-154. doi: 10.1038/s41574-018-0126-x.
Obesity is associated with both increased cancer incidence and progression in multiple tumour types, and is estimated to contribute to up to 20% of cancer-related deaths. These associations are driven, in part, by metabolic and inflammatory changes in adipose tissue that disrupt physiological homeostasis both within local tissues and systemically. However, the mechanisms underlying the obesity-cancer relationship are poorly understood. In this Review, we describe how the adipose tissue microenvironment (ATME) evolves during body-weight gain, and how these changes might influence tumour initiation and progression. We focus on multiple facets of ATME physiology, including inflammation, vascularity and fibrosis, and discuss therapeutic interventions that have the potential to normalize the ATME, which might be translationally relevant for cancer prevention and therapy. Given that the prevalence of obesity is increasing on an international scale, translational research initiatives are urgently needed to provide mechanistic explanations for the obesity-cancer relationship, and how to best identify high-risk individuals without relying on crude measures, such as BMI.
肥胖与多种肿瘤类型的癌症发病率和进展有关，据估计，肥胖导致了多达 20%的癌症相关死亡。这些关联部分是由脂肪组织中的代谢和炎症变化驱动的，这些变化破坏了局部组织和全身的生理平衡。然而，肥胖与癌症之间的关系的机制尚不清楚。在这篇综述中，我们描述了体重增加过程中脂肪组织微环境（ATME）的演变，以及这些变化如何影响肿瘤的发生和发展。我们重点讨论了 ATME 生理学的多个方面，包括炎症、血管生成和纤维化，并讨论了具有潜在转化意义的能够使 ATME 正常化的治疗干预措施，这可能对癌症的预防和治疗具有重要意义。鉴于肥胖的流行程度在国际范围内不断增加，迫切需要开展转化研究计划，以提供肥胖与癌症之间关系的机制解释，以及如何在不依赖 BMI 等粗略指标的情况下，最好地识别高风险个体。
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