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By using in vivo and in vitro brain metastasis models, as well as human samples to study the role of the NLRP3 inflammasome in triple-negative breast cancer (TNBC) brain metastases, we found NLRP3 inflammasome components and IL-1\u03b2 to be highly and specifically expressed in peritumoral astrocytes. Soluble factors from TNBC cells induced upregulation and activation of NLRP3 and IL-1\u03b2 in astrocytes, while astrocyte-derived mediators augmented the proliferation of metastatic cells. In addition, inhibition of NLRP3 inflammasome activity using MCC950 or dampening the downstream effect of IL-1\u03b2 prevented the proliferation increase in cancer cells. In vivo, MCC950 reduced IL-1\u03b2 expression in peritumoral astrocytes, as well as the levels of inflammasome components and active IL-1\u03b2. Most importantly, significantly retarded growth of brain metastatic tumors was observed in mice treated with MCC950. Overall, astrocytes contribute to TNBC progression in the brain through activation of the NLRP3 inflammasome and consequent IL-1\u03b2 release. We conclude that pharmacological targeting of inflammasomes may become a novel strategy in controlling brain metastatic diseases.<\/jats:p>","DOI":"10.1186\/s40478-023-01646-2","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T10:02:53Z","timestamp":1695636173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Inflammasome activation in peritumoral astrocytes is a key player in breast cancer brain metastasis development"],"prefix":"10.1186","volume":"11","author":[{"given":"\u00c1d\u00e1m","family":"M\u00e9sz\u00e1ros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Moln\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Fazakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bern\u00e1t","family":"N\u00f3gr\u00e1di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e9l","family":"L\u00fcvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Dud\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Tiszlavicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila Elek","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n Adorj\u00e1n","family":"Krizbai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2366-7337","authenticated-orcid":false,"given":"Imola","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"1646_CR1","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/nature08021","volume":"459","author":"PD Bos","year":"2009","unstructured":"Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA et al (2009) Genes that mediate breast cancer metastasis to the brain. 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All experimental procedures performed in this study were approved by the Regional Animal Health and Food Control Station of Csongr\u00e1d-Csan\u00e1d County (License Number: XVI.\/764\/2018, issued on May 4, 2018). Details on the ARRIVE Essential 10 items are included in \u201c\n                      \n                      \u201d section and in the figure legends. Human samples were collected in accordance with the approval of the Human Investigation Review Board, University of Szeged (License Numbers: EMLOSEB001, issued on January 31, 2017 and 172\/2022-SZTE RKEB, issued on November 22, 2021), as well as in compliance with the Ethical Principles for Medical Research Involving Human Subjects (World Medical Association Declaration of Helsinki). 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