Kounatidis Dimitris, Vallianou Natalia G, Karampela Irene, Grivakou Evgenia, Dalamaga Maria
Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece.
First Department of Internal Medicine, Sismanogleio General Hospital, Athens 15126, Greece.
Semin Cancer Biol. 2025 Aug;113:130-150. doi: 10.1016/j.semcancer.2025.05.013. Epub 2025 May 22.
Obesity represents a global health challenge, with adipose tissue acting as a highly active endocrine organ that synthesizes and secretes a diverse array of bioactive proteins, known as adipokines. These cell signaling molecules regulate metabolic equilibrium, inflammatory cascades, and immune surveillance, exerting substantial systemic effects. A growing body of evidence has also highlighted their key role in cancer biology, through their intricate impact on oncogenic signaling networks and the tumor microenvironment (TME). The TME, a highly dynamic and heterotypic network composed of malignant cells, infiltrating immune cells, stromal constituents, and extracellular matrix elements, facilitates tumor evolution and immune evasion. Among adipokines, adiponectin and leptin have been extensively studied. Research has shown that adiponectin exhibits tumor-suppressive properties, whereas leptin enhances proliferative, angiogenic, and inflammatory pathways that promote malignancy. However, these effects are context-dependent and, at times, contradictory across different studies. Furthermore, the functional landscape of adipokines in cancer extends beyond these paradigms, with emerging research identifying a broader spectrum of novel adipokines involved in cancer reprogramming. This review delineates the molecular interplay between adipokines and oncogenic pathways, elucidating their mechanistic contributions to TME crosstalk and immune modulation. Additionally, we examine their potential as diagnostic and prognostic biomarkers and assess their viability as therapeutic targets for precision oncology. By integrating current evidence and identifying unresolved questions, this review aims to refine our understanding of adipokine-driven tumor biology and establish a platform for future research.
肥胖是一项全球性的健康挑战，脂肪组织作为一个高度活跃的内分泌器官，能够合成并分泌多种生物活性蛋白，即脂肪因子。这些细胞信号分子调节代谢平衡、炎症级联反应和免疫监视，发挥着重要的全身作用。越来越多的证据还凸显了它们在癌症生物学中的关键作用，它们通过对致癌信号网络和肿瘤微环境（TME）产生复杂影响来发挥作用。肿瘤微环境是一个由恶性细胞、浸润免疫细胞、基质成分和细胞外基质成分组成的高度动态且异型的网络，它促进肿瘤进展和免疫逃逸。在脂肪因子中，脂联素和瘦素已得到广泛研究。研究表明，脂联素具有肿瘤抑制特性，而瘦素则增强促进恶性肿瘤的增殖、血管生成和炎症途径。然而，这些作用取决于具体情况，而且在不同研究中有时相互矛盾。此外，脂肪因子在癌症中的功能格局超出了这些范例，新出现的研究发现了更多参与癌症重编程的新型脂肪因子。本综述阐述了脂肪因子与致癌途径之间的分子相互作用，阐明了它们对肿瘤微环境串扰和免疫调节的机制性贡献。此外，我们研究了它们作为诊断和预后生物标志物的潜力，并评估了它们作为精准肿瘤学治疗靶点的可行性。通过整合现有证据并找出未解决的问题，本综述旨在深化我们对脂肪因子驱动的肿瘤生物学的理解，并建立一个未来研究的平台。
