{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:17:08Z","timestamp":1787807828526,"version":"build-2784847793"},"reference-count":147,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Breast Cancer Now","award":["2024MarDLR1797"],"award-info":[{"award-number":["2024MarDLR1797"]}]},{"award":["2024MarDLR1797"],"award-info":[{"award-number":["2024MarDLR1797"]}],"id":[{"id":"https:\/\/ror.org\/02qa92s63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breast cancer relapse in bone is a significant clinical problem that is experienced in ~70\u201380% of patients with late-stage breast cancer. This condition commonly occurs 5\u201310+ years following surgical removal of the primary tumour. The long latency seen prior to relapse in bone is a result of tumour cell dormancy. Once disseminated to the bone, tumour cell interaction with the bone metastatic niche (endosteal niche and endovascular cells) maintains cells in a dormant state until changes to the local environment activate the niche to support outgrowth. Amassing evidence suggests that cytokines are key regulators of the bone metastatic niche, controlling bone homing and metastatic outgrowth. Pro-inflammatory cytokines, including IL-1\u03b2, IL-6, IL-8, TGF\u03b2 and RANKL, play crucial roles in attracting tumour cells to bone. Furthermore, these cytokines act in conjunction with IFN, VEGF, TGF, PTHrP, FGF, OPG and various chemokines to regulate expansion of the niche, facilitating tumour cell escape from dormancy and promoting the \u201cvicious cycle of bone metastasis\u201d. Here, we review the current literature to provide an up-to-date understanding of how interactions between cytokine signalling cascades regulate the bone metastatic niches to promote homing, dormancy or metastatic outgrowth of breast cancers. Because breast cancers are predominantly osteolytic, this review focuses on dormancy and metastatic outgrowth associated with lytic disease in addition to current advances in novel therapeutics aimed at preventing this condition through targeting dormant cells.<\/jats:p>","DOI":"10.3390\/cells15171528","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:00:48Z","timestamp":1787644848000},"page":"1528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokine Regulation of the Bone Pre- and Metastatic Niches: Implications for Breast Cancer Dormancy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9744-4727","authenticated-orcid":false,"given":"Tamara A.","family":"Clover","sequence":"first","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-4905","authenticated-orcid":false,"given":"Maria L.","family":"Price","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-4186","authenticated-orcid":false,"given":"Lewis A.","family":"Quayle","sequence":"additional","affiliation":[{"name":"School of Biosciences and Chemistry, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Le Maitre","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4826-0771","authenticated-orcid":false,"given":"Penelope D.","family":"Ottewell","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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