Faria Sara Socorro, Corrêa Luís Henrique, Heyn Gabriella Simões, de Sant'Ana Lívia Pimentel, Almeida Raquel das Neves, Magalhães Kelly Grace
Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasilia, Brazil.
J Breast Cancer. 2020 Jun;23(3):233-245. doi: 10.4048/jbc.2020.23.e35.
Obesity is associated with increased risk and aggressiveness of many types of cancer. Women with obesity and breast cancer are more likely to be diagnosed with larger and higher-grade tumors and have higher incidence of metastases than lean individuals. Increasing evidence indicates that obesity includes systemic, chronic low-grade inflammation, and that adipose tissue can act as an important endocrine site, secreting a variety of substances that may regulate inflammation, immune response, and cancer predisposition. Obesity-associated inflammation appears to be initially mediated by macrophage infiltration into adipose tissue. Macrophages can surround damaged or necrotic adipocytes, forming "crown-like" structures (CLS). CLS are increased in breast adipose tissue from breast cancer patients and are more abundant in patients with obesity conditions. Moreover, the CLS index-ratio from individuals with obesity seems to influence breast cancer recurrence rates and survival. In this review, we discuss the most recent cellular and molecular mechanisms involved in CLS establishment in the white adipose tissue of women with obesity and their implications for breast cancer biology. We also explain how CLS influence the tumor microenvironment and affect breast cancer behavior. Targeting breast adipose tissue CLS can be a crucial therapeutic tool in cancer treatment, especially in patients with obesity.
肥胖与多种癌症的风险增加及侵袭性增强相关。肥胖的乳腺癌女性比体型瘦的个体更易被诊断出肿瘤更大、分级更高,且转移发生率更高。越来越多的证据表明,肥胖包含全身性慢性低度炎症,脂肪组织可作为重要的内分泌部位,分泌多种可能调节炎症、免疫反应和癌症易感性的物质。肥胖相关炎症似乎最初由巨噬细胞浸润至脂肪组织介导。巨噬细胞可围绕受损或坏死的脂肪细胞,形成“冠状”结构(CLS)。CLS在乳腺癌患者的乳腺脂肪组织中增多,在肥胖患者中更为丰富。此外,肥胖个体的CLS指数比值似乎会影响乳腺癌复发率和生存率。在本综述中,我们讨论了肥胖女性白色脂肪组织中CLS形成所涉及的最新细胞和分子机制及其对乳腺癌生物学的影响。我们还解释了CLS如何影响肿瘤微环境并影响乳腺癌行为。靶向乳腺脂肪组织CLS可能是癌症治疗尤其是肥胖患者治疗中的关键治疗工具。