Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, United States of America.
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America.
Pharmacol Ther. 2022 Oct;238:108274. doi: 10.1016/j.pharmthera.2022.108274. Epub 2022 Aug 28.
Bone is a frequent site of metastasis from several organs and a host for cancer cells that have originated from the bone marrow itself. Skeletal malignancies are extremely difficult to treat. This is largely due to the complex, heterogenous nature of the bone marrow microenvironment and the dynamic interplay between the tumor cells and multiple cell types within the marrow niche. One cell type whose dominant role in supporting tumor progression and therapy evasion is being increasingly recognized are bone marrow adipocytes (BMAs). BMAs are metabolically active endocrine cells that supply lipids, hormones and adipocytokines to the neighboring cells. Their numbers in bone marrow increase with age, obesity and in response to certain treatments and metabolic conditions. BMAs have been shown to directly promote tumor growth through a transfer of lipids, upregulation of lipid transporters, modulation of tumor metabolism and activation of adaptive stress mechanisms in the cancer cells to promote survival. Less is known, however, regarding how adipocyte interactions with other cell types in the bone tumor microenvironment support malignant progression. This review summarizes recent findings on the crosstalk between BMAs and immune cells in bone. We focus specifically on how adipocyte-mediated changes in the immune milieu impact the tumor cell survival and therapy response. We also discuss how adipocyte-immune cell interactions alter bone homeostasis to support malignant progression in a context of current therapeutic strategies for skeletal malignancies.
骨骼是多种器官转移的常见部位，也是源自骨髓本身的癌细胞的宿主。骨骼恶性肿瘤极难治疗。这主要是由于骨髓微环境的复杂、异质性以及肿瘤细胞与骨髓龛内多种细胞类型之间的动态相互作用。一种细胞类型在支持肿瘤进展和逃避治疗方面的主导作用正越来越受到重视，这就是骨髓脂肪细胞（BMAs）。BMAs 是代谢活跃的内分泌细胞，向邻近细胞提供脂质、激素和脂肪细胞因子。随着年龄的增长、肥胖以及对某些治疗和代谢状况的反应，它们在骨髓中的数量会增加。BMAs 已被证明通过脂质转移、脂质转运蛋白的上调、肿瘤代谢的调节以及激活癌细胞中的适应性应激机制直接促进肿瘤生长，从而促进存活。然而，关于脂肪细胞与骨肿瘤微环境中的其他细胞类型之间的相互作用如何支持恶性进展，人们知之甚少。这篇综述总结了最近关于 BMAs 与骨中免疫细胞之间相互作用的研究发现。我们特别关注脂肪细胞介导的免疫微环境变化如何影响肿瘤细胞的存活和治疗反应。我们还讨论了脂肪细胞-免疫细胞相互作用如何改变骨内稳态，以支持在当前骨骼恶性肿瘤治疗策略背景下的恶性进展。
