Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt A):112911. doi: 10.1016/j.intimp.2024.112911. Epub 2024 Sep 3.
Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.
背景 肥胖是肿瘤发生和发展的独立危险因素。肥胖受脂肪因子信号的影响,脂肪因子是脂肪组织中脂肪细胞和固有免疫细胞分泌的介导脂质代谢的因子。最近,脂肪因子被认为与慢性炎症以及肿瘤的形成和生长有关。其中,抵抗素通过多种信号通路,在与实体瘤和血液系统恶性肿瘤的生长和扩张相关的研究中受到越来越多的关注。
目的和发现 我们回顾了脂肪组织的生理、生化和免疫功能,重点介绍了抵抗素和多种脂肪细胞类型中脂肪因子的结构和表达、它们的信号通路及其对肿瘤细胞的潜在作用,以及它们在体内的调节。目前的证据表明,抵抗素等脂肪因子作为促炎因子,刺激免疫细胞,进而促进肿瘤血管生成、结缔组织增殖和基质纤维化。同时,在肥胖个体代谢功能障碍和脂肪毒性状态下,免疫细胞的数量和功能受损,导致免疫抑制环境,促进肿瘤细胞存活和癌症免疫监测减弱。
结论 抵抗素等脂肪因子对肥胖相关肿瘤的发生发展至关重要。阐明与肥胖相关的因素在免疫调节和肿瘤进展中的作用,可能会发现针对肥胖因子(如抵抗素)的新型抗肿瘤策略,以限制肿瘤生长并控制肥胖,或两者兼而有之。