{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:41:57Z","timestamp":1791549717312,"version":"4.3.4"},"reference-count":99,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_204345"],"award-info":[{"award-number":["310030_204345"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extracellular matrix (ECM) remodeling plays critical roles in cancer progression and involves alterations in its composition and biophysical properties. Aggressiveness and malignancy of solid tumors are strongly correlated with tissue stiffening, mainly due to upregulated ECM production and cross\u2010linking. However, nothing is known about the tensional alterations that occur at the single\u2010fiber level during tumorigenesis in humans. The well\u2010validated peptide tension probe (FnBPA5) now reveals that Fibronectin fibers lose their tension as invasive tumors progress while they are stretched in healthy human breast tissue stroma and in ductal carcinoma in situ (DCIS), the non\u2010invasive precursor of breast cancer. In invasive carcinomas, cancer cells, cancer\u2010associated fibroblasts (CAFs) and infiltrating immune cells (cytotoxic T cells and regulatory T cells), are predominantly located in proximity to untensed Fibronectin fibers. This is significant, as Fibronectin fiber stretching can mechano\u2010regulate the reciprocal cell\u2010ECM crosstalk and the bioavailability of ECM\u2010bound molecules. Not only tissue stiffening, but also the accumulation of untensed Fibronectin fibers may serve as a mechanical biomarker that correlates with tumor grade. Loss of Fibronectin fiber tension may play a central role in regulating tumor invasiveness. This suggests that physically altered ECM fibers can be exploited for stroma\u2010targeted drug delivery and immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.202404351","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:08:22Z","timestamp":1749726502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fibronectin Fibers Progressively Lose Their Tension in Invasive Human Breast Carcinoma while Being Tensed in DCIS and Healthy Breast Tissue"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2662-4888","authenticated-orcid":false,"given":"Arnaud","family":"Mi\u00e9ville","sequence":"first","affiliation":[{"name":"Laboratory of Applied Mechanobiology Institute of Translational Medicine Department of Health Sciences and Technology  ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Fonta","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Mechanobiology Institute of Translational Medicine Department of Health Sciences and Technology  ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Leo","sequence":"additional","affiliation":[{"name":"Breast Center Department of Gynecology  Kantonsspital Baden Baden Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucine","family":"Christe","sequence":"additional","affiliation":[{"name":"Institute of Tissue Medicine and Pathology University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Goldhahn","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine Department of Health Sciences and Technology  ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Singer","sequence":"additional","affiliation":[{"name":"Institute of Pathology  Kantonsspital Baden Baden Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2898-7671","authenticated-orcid":false,"given":"Viola","family":"Vogel","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Mechanobiology Institute of Translational Medicine Department of Health Sciences and Technology  ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2015.01.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18794-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-061421-035400"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2019.00160"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.16901"},{"key":"e_1_2_9_8_1","author":"Wang S.","year":"2024","journal-title":"Cancer Pathogenesis and Therapy"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00656-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz0868"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-023-02992-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188356"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-13-0535"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2544"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.027"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2612-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.076"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-025-00727-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-071813-105259"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2012.167"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.18650"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11020088"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3937"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5ib00040h"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694912"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2017.04.005"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-4-38"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-016-9650-0"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-17-0720"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-20-0889"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907518106"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021317-121312"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b02755"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1135"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2023.12.006"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9026"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00641"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.03.006"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-019-09966-1"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.7b01617"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1351"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271015"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112788"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.261483"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.299"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439246"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051046"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31126-w"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.015"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.004077"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01846-0"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/nl302153h"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072650799"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050268"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.09.028"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2020.100046"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2023.01.002"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2022.02.007"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636108"},{"key":"e_1_2_9_60_1","author":"Brierley J. D.","year":"2017","journal-title":"TNM classification of malignant tumours \u20138th Edition"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.4161\/19336918.2014.994901"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.002"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2016.12.010"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-012-1289-9"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00348"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70262-1"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1159\/isbn.978-3-318-06141-3"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051532"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111185"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/36.6.3367051"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4414"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1991.tb00229.x"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-20-0074"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1808"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00329-7"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000127"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.73"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3218"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.05.008"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.03.019"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133285"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100937"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58688"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62954-9"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114240"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(01)00197-4"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0223-z"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0038-z"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201302041"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176009"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2019.06.001"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1022808"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74433"},{"key":"e_1_2_9_96_1","first-page":"1370","volume":"11","author":"Morello A.","year":"2023","journal-title":"J Immunother Cancer"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-015-0417-4"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0056195"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-28549-8_3"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202404351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:36:55Z","timestamp":1759750615000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202404351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,5]]},"references-count":99,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/advs.202404351"],"URL":"https:\/\/doi.org\/10.1002\/advs.202404351","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,5]]},"assertion":[{"value":"2024-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04351"}}