Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Cancer Metastasis Rev. 2022 Sep;41(3):627-647. doi: 10.1007/s10555-022-10031-9. Epub 2022 Apr 18.
Women with obesity who develop breast cancer have a worsened prognosis with diminished survival rates and increased rates of metastasis. Obesity is also associated with decreased breast cancer response to endocrine and chemotherapeutic treatments. Studies utilizing multiple in vivo models of obesity as well as human breast tumors have enhanced our understanding of how obesity alters the breast tumor microenvironment. Changes in the complement and function of adipocytes, adipose-derived stromal cells, immune cells, and endothelial cells and remodeling of the extracellular matrix all contribute to the rapid growth of breast tumors in the context of obesity. Interactions of these cells enhance secretion of cytokines and adipokines as well as local levels of estrogen within the breast tumor microenvironment that promote resistance to multiple therapies. In this review, we will discuss our current understanding of the impact of obesity on the breast tumor microenvironment, how obesity-induced changes in cellular interactions promote resistance to breast cancer treatments, and areas for development of treatment interventions for breast cancer patients with obesity.
肥胖女性罹患乳腺癌后，预后较差，生存率降低，转移率增加。肥胖还与乳腺癌对内分泌和化疗治疗的反应降低有关。利用多种肥胖的体内模型以及人类乳腺癌肿瘤的研究，增强了我们对肥胖如何改变乳腺肿瘤微环境的理解。补体和脂肪细胞、脂肪衍生基质细胞、免疫细胞和内皮细胞的功能的改变，以及细胞外基质的重塑，都导致肥胖情况下乳腺肿瘤的快速生长。这些细胞的相互作用增强了细胞因子和脂肪因子的分泌，以及乳腺肿瘤微环境中局部雌激素水平，从而促进了对多种治疗的耐药性。在这篇综述中，我们将讨论我们目前对肥胖对乳腺肿瘤微环境的影响的理解，肥胖引起的细胞相互作用的变化如何促进乳腺癌治疗的耐药性，以及为肥胖乳腺癌患者的治疗干预措施的发展领域。
