Department of Oncology and Metabolism, University of Sheffield, Beech Hill Road, SheffieldS10 2RX, UK.
Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität (WWU), 48149Münster, Germany.
Expert Rev Mol Med. 2022 Mar 1;24:e11. doi: 10.1017/erm.2022.4.
Bone is the most common site for advanced breast cancer to metastasise. The proinflammatory cytokine, interleukin-1β (IL-1β) plays a complex and contradictory role in this process. Recent studies have demonstrated that breast cancer patients whose primary tumours express IL-1β are more likely to experience relapse in bone or other organs. Importantly, IL-1β affects different stages of the metastatic process including growth of the primary tumour, epithelial to mesenchymal transition (EMT), dissemination of tumour cells into the blood stream, tumour cell homing to the bone microenvironment and, once in bone, this cytokine participates in the interaction between cancer cells and bone cells, promoting metastatic outgrowth at this site. Interestingly, although inhibition of IL-1β signalling has been shown to have potent anti-metastatic effects, inhibition of the activity of this cytokine has contradictory effects on primary tumours, sometimes reducing but often promoting their growth. In this review, we focus on the complex roles of IL-1β on breast cancer bone metastasis: specifically, we discuss the distinct effects of IL-1β derived from tumour cells and/or microenvironment on inhibition/induction of primary breast tumour growth, induction of the metastatic process through the EMT, promotion of tumour cell dissemination into the bone metastatic niche and formation of overt metastases.
骨骼是晚期乳腺癌转移最常见的部位。促炎细胞因子白细胞介素-1β（IL-1β）在这个过程中发挥着复杂而矛盾的作用。最近的研究表明，原发肿瘤表达 IL-1β的乳腺癌患者更有可能在骨骼或其他器官中复发。重要的是，IL-1β 影响转移过程的不同阶段，包括原发肿瘤的生长、上皮间质转化（EMT）、肿瘤细胞进入血流的扩散、肿瘤细胞向骨骼微环境的归巢，以及一旦进入骨骼，这种细胞因子就参与癌细胞和骨细胞之间的相互作用，促进该部位的转移性生长。有趣的是，尽管抑制 IL-1β 信号已被证明具有强大的抗转移作用，但抑制这种细胞因子的活性对原发肿瘤有相反的影响，有时会抑制其生长，但通常会促进其生长。在这篇综述中，我们重点讨论了 IL-1β 对乳腺癌骨转移的复杂作用：具体来说，我们讨论了肿瘤细胞和/或微环境产生的 IL-1β 对抑制/诱导原发性乳腺癌生长、通过 EMT 诱导转移过程、促进肿瘤细胞扩散到骨转移龛位以及形成明显转移的不同影响。
