Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada.
Centre de recherche du Centre hospitalier universitaire de Sherbrooke, CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada.
Cancer Metastasis Rev. 2021 Jun;40(2):427-445. doi: 10.1007/s10555-021-09974-2. Epub 2021 May 11.
Breast and prostate cancers have a great propensity to metastasize to long bones. The development of bone metastases is life-threatening, incurable, and drastically reduces patients' quality of life. The chemokines CCL2 and CXCL12 and their respective receptors, CCR2 and CXCR4, are central instigators involved in all stages leading to cancer cell dissemination and secondary tumor formation in distant target organs. They orchestrate tumor cell survival, growth and migration, tumor invasion and angiogenesis, and the formation of micrometastases in the bone marrow. The bone niche is of particular importance in metastasis formation, as it expresses high levels of CCL2 and CXCL12, which attract tumor cells and contribute to malignancy. The limited number of available effective treatment strategies highlights the need to better understand the pathophysiology of bone metastases and reduce the skeletal tumor burden in patients diagnosed with metastatic bone disease. This review focuses on the involvement of the CCL2/CCR2 and CXCL12/CXCR4 chemokine axes in the formation and development of bone metastases, as well as on therapeutic perspectives aimed at targeting these chemokine-receptor pairs.
乳腺癌和前列腺癌具有向长骨转移的强烈倾向。骨转移的发展是危及生命的、不可治愈的，并大大降低了患者的生活质量。趋化因子 CCL2 和 CXCL12 及其各自的受体 CCR2 和 CXCR4 是参与导致癌细胞扩散和继发性肿瘤在远处靶器官形成的所有阶段的核心启动子。它们协调肿瘤细胞的存活、生长和迁移、肿瘤侵袭和血管生成，以及骨髓中微转移的形成。骨基质在转移形成中尤为重要，因为它表达高水平的 CCL2 和 CXCL12，吸引肿瘤细胞并促进恶性程度。现有的有效治疗策略数量有限，这突出表明需要更好地了解骨转移的病理生理学，并减少诊断为转移性骨病的患者的骨骼肿瘤负担。本综述重点介绍了趋化因子 CCL2/CCR2 和 CXCL12/CXCR4 轴在骨转移的形成和发展中的作用，以及针对这些趋化因子-受体对的治疗观点。
