癌症干细胞（CSCs）是肿瘤内高度致瘤亚群中的癌细胞，驱动肿瘤的起始、进展和治疗抵抗。一般而言，干细胞微环境为干细胞提供了一种特殊的微环境，使干细胞保持未分化和自我更新的状态。CSC微环境是一种专门为CSC提供信号以维持和传播的肿瘤微环境。然而，CSC-微环境相互作用的分子机制还有待阐明。我们已揭示腺脂酸（补体因子D）及其下游效应子肝细胞生长因子从脂肪细胞分泌并增强了乳腺癌中CSC的特性，其中肿瘤的起始和进展与周围脂肪组织密切相关。考虑到肥胖性与多种癌症的风险增加有关，而肥胖性特征为脂肪组织过多，合理可推测脂肪细胞-CSC相互作用同样参与了多种癌症，如胰腺癌、结直肠癌和卵巢癌。本综述讨论了脂肪细胞调控CSC的各种分子机制，包括脂肪因子的分泌、细胞外基质的产生、雌激素的生物合成、新陈代谢和外泌体。发现脂肪细胞在CSC微环境中的作用将提出治疗癌症的新策略，特别是那些与肥胖有关的癌症的进展。© 2023 The Authors. 由John Wiley＆Sons Australia, Ltd代表日本癌症协会出版的《Cancer Science》发表。

Cancer stem cells (CSCs) are a highly tumorigenic subpopulation of the cancer cells within a tumor that drive tumor initiation, progression, and therapy resistance. In general, stem cell niche provides a specific microenvironment in which stem cells are present in an undifferentiated and self-renewable state. CSC niche is a specialized tumor microenvironment for CSCs which provides cues for their maintenance and propagation. However, molecular mechanisms for the CSC-niche interaction remain to be elucidated. We have revealed that adipsin (complement factor D) and its downstream effector hepatocyte growth factor are secreted from adipocytes and enhance the CSC properties in breast cancers in which tumor initiation and progression are constantly associated with the surrounding adipose tissue. Considering that obesity, characterized by excess adipose tissue, is associated with an increased risk of multiple cancers, it is reasonably speculated that adipocyte-CSC interaction is similarly involved in many types of cancers, such as pancreas, colorectal, and ovarian cancers. In this review, various molecular mechanisms by which adipocytes regulate CSCs, including secretion of adipokines, extracellular matrix production, biosynthesis of estrogen, metabolism, and exosome, are discussed. Uncovering the roles of adipocytes in the CSC niche will propose novel strategies to treat cancers, especially those whose progression is linked to obesity.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.