{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:25Z","timestamp":1783574125772,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor-resident mesenchymal stem\/stromal cells (MSCs) were identified in several cancers, and were implicated in regulating multiple aspects of tumor progression. However, the role of tumor-resident MSCs in the pathophysiology of brain metastases (BrMs) -the most prevalent type of malignant brain tumor- is currently unknown, and was investigated in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tumor-resident MSCs were isolated from fresh human lung-BrM tissues (n=3) and were phenotypically assessed in FFPE lung-BrM tissues (n=11). The paracrine effects of BrM-MSCs on neutrophil granulocytes and endothelial cells (ECs) were examined in\n                      <jats:italic>ex vivo<\/jats:italic>\n                      models using MSC-derived supernatants (SNs), peripheral blood neutrophils from healthy donors and two different EC models (HUVEC and HCAEC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The isolated BrM-MSCs were characterized and validated according to the ISCT\n                      <jats:sup>\u00ae<\/jats:sup>\n                      criteria. Cells with an MSC-like phenotype were also identified\n                      <jats:italic>in situ<\/jats:italic>\n                      , in the majority of the samples analyzed (9 out of 11). The MSC-derived SNs promoted neutrophil chemotaxis, and prolonged their survival. Additionally, BrM-MSC SNs stimulated neutrophils to release significant levels of pro-angiogenic and pro-invasive matrix metalloprotease (MMP) 9. In contrast, BrM-MSC SNs had no direct stimulatory effect on the ECs regarding MMP2 release, migration and proliferation, and even inhibited the tubulogenesis in HUVEC. However, the latter effect could not be validated with the HCAEC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results indicate that BrMs harbor tumor-resident MSCs that modulate neutrophil biology and function within the BrM microenvironment. While the direct effects of BrM-MSCs on ECs remain to be further characterized, tumor-resident MSCs may play critical roles in the pathophysiology of this disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1891707","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:18Z","timestamp":1783570998000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The paracrine effects of tumor-resident mesenchymal stem\/stromal cells in the microenvironment of brain metastases"],"prefix":"10.3389","volume":"16","author":[{"given":"Tamer Ayberk","family":"Kaya","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Peter","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belal","family":"Neyazi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Rashidi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf Dietrich","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General-, Visceral-, Vascular- and Transplantation Surgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]},{"name":"Research Campus STIMULATE, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mawrin","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Erol","family":"Sandalcioglu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Alexandra","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Otto-von-Guericke University","place":["Magdeburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-811161-1.00002-5","article-title":"Brain metastases: epidemiology","volume":"149","author":"Ostrom","year":"2018","journal-title":"Handb Clin Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00781","article-title":"Tumor primary site and histology subtypes role in radiotherapeutic management of brain metastases","volume":"10","author":"Khan","year":"2020","journal-title":"Front Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s12672-025-01873-0","article-title":"Brain metastases from lung cancer: recent advances and novel therapeutic opportunities","volume":"16","author":"Layng","year":"2025","journal-title":"Discov Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/Jco.2011.38.0527","article-title":"Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases","volume":"30","author":"Sperduto","year":"2012","journal-title":"J Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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