{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:46:47Z","timestamp":1785887207486,"version":"3.56.0"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["GAUK 342522"],"award-info":[{"award-number":["GAUK 342522"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU22\u201003\u201000318"],"award-info":[{"award-number":["NU22\u201003\u201000318"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["EATRIS\u2010CZ LM2023053"],"award-info":[{"award-number":["EATRIS\u2010CZ LM2023053"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Brain metastases (BrM) are a frequent and life\u2010threatening complication of solid tumours, with lung cancer representing their most common source. While cancer\u2010associated fibroblasts (CAFs) are well\u2010established contributors to tumour progression in many extracranial malignancies, their presence and function within the brain tumour microenvironment, where fibroblasts have long been considered scarce or absent, remain poorly understood. Here, we isolated and characterised fibroblast\u2010like cells from 13 human BrMs of diverse origins. These BrM\u2010associated CAFs (BrM\u2010CAFs) expressed canonical CAF markers and showed reduced proliferation and increased senescence compared to normal fibroblasts. Their transcriptome was enriched for extracellular matrix (ECM)\u2010related genes, including multiple collagens, fibronectin, and matrix\u2010remodelling enzymes. In vitro, BrM\u2010CAFs produced a fibrillar ECM, and in BrM tissues, their abundance was associated with collagen I and fibronectin deposition. Transcriptomic, proteomic, and secretome analyses further revealed that BrM\u2010CAFs produce multiple cytokines, chemokines, and growth factors that promote cell motility. BrM\u2010CAF conditioned medium promoted both monocyte migration and the migration of cancer cells, including established cell lines and patient\u2010derived lung cancer BrM cells; monocyte migration was partially reduced by inhibition of CCL2\/CCR2 signalling, whereas blocking CXCL12, CXCL16, or CX3CL1 attenuated BrM\u2010CAF\u2010induced cancer cell migration. Beyond these effects on migration, exposure to BrM\u2010CAFs increased cancer cell invasion in transwell and heterotypic 3D spheroid assays. In contrast, their effects on cancer cell proliferation were limited and did not indicate a growth\u2010promoting role. Exposure to BrM\u2010CAFs was also associated with increased expression of interferon\u2010stimulated genes in cancer cells. Together, our findings support a role for BrM\u2010CAFs in shaping the brain metastatic microenvironment through ECM remodelling and the secretion of pro\u2010migratory mediators, promoting monocyte and cancer cell migration and enhancing cancer cell invasion. These data identify BrM\u2010CAFs as active stromal participants in BrM biology and support further investigation of their biological, diagnostic, and therapeutic relevance.<\/jats:p>","DOI":"10.1111\/bpa.70129","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:00:07Z","timestamp":1785884407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain metastasis\u2010associated fibroblasts shape the tumour microenvironment to enhance cancer cell invasion"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6100-1125","authenticated-orcid":false,"given":"Barbora","family":"V\u00fdmolov\u00e1","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Pfeiferov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences  Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5419-0665","authenticated-orcid":false,"given":"Tade\u00e1\u0161 Karel","family":"Smetana","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"V\u00fdmola","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7825-3735","authenticated-orcid":false,"given":"Nikola","family":"Ternerov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-6185","authenticated-orcid":false,"given":"Michal","family":"Zuba\u013e","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-1525","authenticated-orcid":false,"given":"Michal","family":"Kol\u00e1\u0159","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences  Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-6127","authenticated-orcid":false,"given":"Jana","family":"\u0160\u00e1chov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences  Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u0148a","family":"Gy\u00f6ny\u00f6rov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bal\u00e1\u017eiov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Houdov\u00e1 Megov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-2045","authenticated-orcid":false,"given":"Jakub","family":"\u010cervenka","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-5018","authenticated-orcid":false,"given":"Helena","family":"Kupcov\u00e1 Skaln\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"\u0160panko","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7878-8403","authenticated-orcid":false,"suffix":"Jr.","given":"Karel","family":"Smetana","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-9933","authenticated-orcid":false,"given":"Luk\u00e1\u0161","family":"Lacina","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, First Faculty of Medicine Charles University  Prague 2 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Netuka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, First Faculty of Medicine Charles University and Military University Hospital  Prague 6 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Tom\u00e1\u0161","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Motol and Homolka University Hospital  Prague 5 Czech 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