Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
3rd Orthopaedic and Traumatologic Clinic Prevalently Oncologic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Front Endocrinol (Lausanne). 2023 Aug 29;14:1207416. doi: 10.3389/fendo.2023.1207416. eCollection 2023.
Bone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.
A comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, to identify studies published from March 2013 to June 2023. Two independent reviewers assessed and screened the literature, extracted the data, and evaluated the quality of the studies. The body of evidence was evaluated and graded using the ROBINS-I tool for non-randomized studies of interventions and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool for studies. The results were synthesized using descriptive methods.
The search yielded a total of 463 studies, of which 17 studies were included in the final analysis, including 15 preclinical studies and two non-randomized clinical studies. Analysis of preclinical studies revealed that BMAs play a significant role in bone metastasis, particularly in prostate cancer followed by breast and malignant melanoma cancers. BMAs primarily influence cancer cells by inducing a glycolytic phenotype and releasing or upregulating soluble factors, chemokines, cytokines, adipokines, tumor-derived fatty acid-binding protein (FABP), and members of the nuclear receptor superfamily, such as chemokine (C-C motif) ligand 7 (CCL7), C-X-C Motif Chemokine Ligand (CXCL)1, CXCL2, interleukin (IL)-1β, IL-6, FABP4, and peroxisome proliferator-activated receptor γ (PPARγ). These factors also contribute to adipocyte lipolysis and regulate a pro-inflammatory phenotype in BMAs. However, the number of clinical studies is limited, and definitive conclusions cannot be drawn.
The preclinical studies reviewed indicate that BMAs may play a crucial role in bone metastasis in prostate, breast, and malignant melanoma cancers. Nevertheless, further preclinical and clinical studies are needed to better understand the complex role and relationship between BMAs and cancer cells in the bone microenvironment. Targeting BMAs in combination with standard treatments holds promise as a potential therapeutic strategy for bone metastasis.
骨髓脂肪细胞（BMAs）是骨髓中最丰富的细胞，通过产生脂肪酸、细胞因子和脂肪因子，充当内分泌器官。因此，BMAs 可以与肿瘤细胞相互作用，影响肿瘤生长以及骨转移的发生和进展。本综述旨在系统评估 BMAs 在骨转移发生和进展中的作用。
根据系统评价和荟萃分析（PRISMA）声明标准，全面检索 PubMed、Web of Science 和 Scopus 电子数据库，以确定 2013 年 3 月至 2023 年 6 月发表的研究。两名独立评审员评估和筛选文献、提取数据并评估研究质量。使用非随机干预研究的 ROBINS-I 工具和用于实验室动物实验的系统评价中心（SYRCLE）工具评估证据体，并对研究进行分级。使用描述性方法综合结果。
检索共得到 463 项研究，其中 17 项研究纳入最终分析，包括 15 项临床前研究和 2 项非随机临床研究。临床前研究分析表明，BMAs 在骨转移中发挥重要作用，特别是在前列腺癌后其次是乳腺癌和恶性黑色素瘤。BMAs 主要通过诱导糖酵解表型和释放或上调可溶性因子、趋化因子、细胞因子、脂肪因子、肿瘤衍生脂肪酸结合蛋白（FABP）和核受体超家族成员（如趋化因子（C-C 基序）配体 7（CCL7）、C-X-C 基序趋化因子配体（CXCL）1、CXCL2、白细胞介素（IL）-1β、IL-6、FABP4 和过氧化物酶体增殖物激活受体 γ（PPARγ））来影响肿瘤细胞。这些因子还参与脂肪细胞脂肪分解，并调节 BMAs 中的促炎表型。然而，临床研究的数量有限，无法得出明确的结论。
综述的临床前研究表明，BMAs 可能在前列腺癌、乳腺癌和恶性黑色素瘤的骨转移中发挥关键作用。然而，需要进一步的临床前和临床研究来更好地了解 BMAs 和癌细胞在骨微环境中的复杂作用和关系。靶向 BMAs 结合标准治疗可能成为骨转移的潜在治疗策略。
