{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T07:14:02Z","timestamp":1788160442838,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":241,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020469","name":"Universidad Cient\u00edfica del Sur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020469","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Analytical Cellular Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>There is no specific therapy for triple\u2010negative breast cancer (TNBC), and the recurrence rate is high. Cancer stem cells (CSCs) play an important role in cancer chemoresistance and metastasis, but there is no consensus marker in this type of cancer. The aim of this study was to identify CSC biomarkers in the plasma secretome of TNBC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CD44+\/CD24\u2212 CSCs were isolated from MDA\u2010MB\u2010436 and MDA\u2010MB\u2010231 (ATCC) lines by magnetic immunoselection. The extracellular vesicles (EVs) of CSCs were isolated by size exclusion chromatography (SEC) of conditioned medium (CM) without fetal bovine serum (FBS) and blood plasma from TNBC and healthy women. Tetraspanins CD9 and CD81 identified the EVs, while electron microscopy determined the morphology and tunable resistive pulse sensing (TRPS) established particle size. Luminex technology was used to determine the presence of L1 cell adhesion molecule (L1CAM), carbonic anhydrase IX (CA9), mesothelin, midkine, hepsin, kallikrein\u20106 (KLK6), transglutaminase 2 (TGM2), aldehyde dehydrogenase 1a1 (ALDH1A1), epithelial cell adhesion molecule (EpCAM), and differentiation cluster 44 (CD44).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Particles of 0\u2013200\u2009nm in size were more frequent in CSC\u2010MDA\u2010MB\u2010436, while particles of 201\u2013500\u2009nm were more frequent in CSC\u2010MDA\u2010MB\u2010231. In blood plasma, the particle size was 150\u2013250\u2009nm in TNBC patients and 150\u2013300\u2009nm in healthy individuals. Particle concentrations were 1.3\u2009\u00d7\u200910\n                      <jats:sup>10<\/jats:sup>\n                      in CSCs of the MDA\u2010MB\u2010231 (CSC\u2010MDA\u2010MB\u2010231) cell line and 3.8\u2009\u00d7\u200910\n                      <jats:sup>7<\/jats:sup>\n                      in the MDA\u2010MB\u2010231 cell line (L\u2010MDA\u2010MB\u2010231). The concentration of CSCs in MDA\u2010MB\u2010436 was 2.7\u2009\u00d7\u200910\n                      <jats:sup>8<\/jats:sup>\n                      compared to 9.4\u2009\u00d7\u200910\n                      <jats:sup>7<\/jats:sup>\n                      in L\u2010MDA\u2010MB\u2010436. Midkine and CA9 were present in the EVs of both CSC lines and in the plasma of women with TNBC but absent in the blood plasma of healthy women. Midkine showed better statistical discrimination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The size and concentration of EVs are heterogeneous. Midkine and CA9 are produced by CSCs in women with TNBC and may be possible biomarkers of these cells in this tumour type.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ancp\/3265988","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:22:42Z","timestamp":1788157362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Midkine and CA9 Are Potential Cancer Stem Cell Biomarkers in Triple\u2010Negative Breast 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