Chkourko Gusky H, Diedrich J, MacDougald O A, Podgorski I
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Obes Rev. 2016 Nov;17(11):1015-1029. doi: 10.1111/obr.12450. Epub 2016 Jul 19.
A number of clinical studies have linked adiposity with increased cancer incidence, progression and metastasis, and adipose tissue is now being credited with both systemic and local effects on tumour development and survival. Adipocytes, a major component of benign adipose tissue, represent a significant source of lipids, cytokines and adipokines, and their presence in the tumour microenvironment substantially affects cellular trafficking, signalling and metabolism. Cancers that have a high predisposition to metastasize to the adipocyte-rich host organs are likely to be particularly affected by the presence of adipocytes. Although our understanding of how adipocytes influence tumour progression has grown significantly over the last several years, the mechanisms by which adipocytes regulate the metastatic niche are not well-understood. In this review, we focus on the omentum, a visceral white adipose tissue depot, and the bone, a depot for marrow adipose tissue, as two distinct adipocyte-rich organs that share common characteristic: they are both sites of significant metastatic growth. We highlight major differences in origin and function of each of these adipose depots and reveal potential common characteristics that make them environments that are attractive and conducive to secondary tumour growth. Special attention is given to how omental and marrow adipocytes modulate the tumour microenvironment by promoting angiogenesis, affecting immune cells and altering metabolism to support growth and survival of metastatic cancer cells.
多项临床研究已将肥胖与癌症发病率增加、进展和转移联系起来,现在脂肪组织被认为对肿瘤的发生发展和生存具有全身和局部影响。脂肪细胞是良性脂肪组织的主要成分,是脂质、细胞因子和脂肪因子的重要来源,它们在肿瘤微环境中的存在会显著影响细胞运输、信号传导和代谢。极易转移至富含脂肪细胞的宿主器官的癌症可能会特别受到脂肪细胞存在的影响。尽管在过去几年里,我们对脂肪细胞如何影响肿瘤进展的理解有了显著增长,但脂肪细胞调节转移小生境的机制仍未得到充分了解。在这篇综述中,我们聚焦于大网膜(一种内脏白色脂肪组织库)和骨骼(骨髓脂肪组织的储存部位),这两个富含脂肪细胞的不同器官具有共同特征:它们都是显著转移性生长的部位。我们强调了这些脂肪库在起源和功能上的主要差异,并揭示了潜在的共同特征,这些特征使它们成为吸引并有利于继发性肿瘤生长的环境。我们特别关注大网膜和骨髓脂肪细胞如何通过促进血管生成、影响免疫细胞和改变代谢来调节肿瘤微环境,以支持转移性癌细胞的生长和存活。