脂肪细胞与肿瘤转移的关系研究进展

Research progress on the relationship between adipocytes and tumor metastasis

肥胖是威胁人们健康的主要慢性疾病之一,主要由脂肪组织扩增引起。在人体,脂肪组织是一个动态的内分泌器官,负责能量稳态。过度肥胖通常会导致代谢紊乱、类固醇激素分泌改变、慢性亚临床炎症以及增加多种肿瘤的发病风险。肿瘤细胞与脂肪细胞的微环境之间存在密切关系,一方面,脂肪细胞来源的细胞因子,如趋化因子配体2、白介素⁃6、肿瘤坏死因子α、瘦素和脂联素等,可通过激活不同的信号通路促进肿瘤的侵袭转移能力;脂肪细胞来源的游离脂肪酸及脂滴可通过FABP4、CD36等转运蛋白转移到肿瘤细胞中,提高肿瘤β氧化速率,产生大量能量,促进肿瘤细胞分裂增殖;另一方面,脂肪细胞可使Treg细胞、CD8+细胞毒性T细胞、巨噬细胞发生代谢重编程,促进Treg细胞及M2型巨噬细胞增殖,抑制CD8+细胞毒性T细胞杀肿瘤活性,从而导致肿瘤免疫逃逸;使中性粒细胞重编程,破坏血管内皮细胞的黏附,导致血管壁渗透性增加,有利于肿瘤细胞穿过血管壁,转移到远处。本文主要探究脂肪细胞与肿瘤转移的关系,旨在为肿瘤治疗提供新的靶点。

Obesity is one of the major chronic diseases threatening people′s health,which is mainly caused by the expansion of adipose tissue.In the human body,adipose tissue is a dynamic endocrine organ responsible for energy homeostasis.Obesity is associated with metabolic disorders,altered steroid secretion,chronic subclinical inflammation,and an increased risk of many cancers.Tumor cells are closely related to adipocytes in microenvironment,on the one hand,adipocyte⁃derived cytokines,such as IL⁃6,CCL2,TNF-α,leptin and adiponectin,can promote tumor invasion and metastasis through activation of different signaling pathways.Free fatty acids and lipid droplets derived from adipocytes can be transferred to tumor cells through FABP4,CD36 and other transporters,which can increase the rate of tumorβoxidation,produce a lot of ATP,and promote the division and proliferation of tumor cells.On the other hand,adipocytes can induce metabolic reprogramming of Treg cells,CD8+cytotoxic T cells and macrophages,promote the proliferation of Treg cells and M2⁃type macrophages,inhibit the tumor⁃killing activity of CD8+cytotoxic T cells,and lead to tumor immune escape.The reprogramming of neutrophils disrupts the adhesion of vascular endothelial cells and leads to increased vascular wall permeability,which is conducive to the passage of tumor cells through the vascular wall and metastasis to distant places.This review mainly explores the relationship between adipocytes and tumor metastasis,aiming to provide new targets for tumor therapy.