{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:48:25Z","timestamp":1776167305266,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21cm0106203h0006"],"award-info":[{"award-number":["21cm0106203h0006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spread through air spaces (STAS) is a histological finding of lung tumours where tumour cells exist within the air space of the lung parenchyma beyond the margin of the main tumour. Although STAS is an important prognostic factor, the pathobiology of STAS remains unclear. Here, we investigated the mechanism of STAS by analysing the relationship between STAS and polarity switching\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Histopathological analysis revealed that apical membranes were observed outside the STAS lesions around colorectal cancer (CRC) lung metastases and lung adenocarcinomas. When apical\u2010out CRC organoids were administered intratracheally to mice, the organoids had greater metastatic potential than did single cells. To investigate the pathobiology of STAS, we established an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of STAS in which CRC or lung cancer organoids were co\u2010cultured with 2D\u2010cultured mouse airway epithelial organoids (2D\u2010MAOs). Adhesion of cancer organoids to 2D\u2010MAOs was much less than to type I collagen or endothelial cells, suggesting a protective role of the airway epithelium against adhesion. Loss of the apical membrane of CRC organoids at the contact surface with 2D\u2010MAOs after adhesion was responsible for establishing adhesion. When airway epithelium was stimulated by transforming growth factor beta 1 (TGF\u2010\u03b21), adhesion of CRC organoids was enhanced. Among TGF\u2010\u03b21\u2010induced genes in airway epithelium, follistatin\u2010like protein 1 (FSTL1) increased CRC organoid adhesion by promoting loss of the apical membrane. These results suggested that TGF\u2010\u03b21\u2010induced FSTL1 may promote metastatic progression of STAS by altering the polarity status. Elucidating the mechanism of STAS could contribute to the improvement of survival in patients with pulmonary malignancies associated with STAS. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6382","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:33:26Z","timestamp":1736760806000},"page":"260-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamic change of polarity in spread through air spaces of pulmonary malignancies"],"prefix":"10.1002","volume":"265","author":[{"given":"Yoshiaki","family":"Matsuura","sequence":"first","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunishige","family":"Onuma","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Coppo","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"KBBM Inc.  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-0480","authenticated-orcid":false,"given":"Jumpei","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"Department of Molecular Biology and Clinical Investigation, Graduate School of Medicine Osaka University  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Miyagawa\u2010Hayashino","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-3352","authenticated-orcid":false,"given":"Naoko","family":"Takeda\u2010Miyata","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kameyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"},{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Furuya","sequence":"additional","affiliation":[{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Okada","sequence":"additional","affiliation":[{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-9479","authenticated-orcid":false,"given":"Masanori","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Divison of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7315-026X","authenticated-orcid":false,"given":"Masahiro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Clinical Bio\u2010resource Research and Development, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.10.020"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.11.003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000486"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02230-w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2022.11.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2018.12.21"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.08.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2004.12.033"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14062"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2020.09.010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.07.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.12.011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5748"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15493"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100300"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13075"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540205000104"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00658-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb5943"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507294112"},{"key":"e_1_2_8_23_1","article-title":"Pre\u2010conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment","author":"Stevens LE","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.11.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.12.021"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2805-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0695-6"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.259256"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00014-10"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2020.01.112"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.069468"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15882"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.021"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36863-1"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-23-0004"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015938108"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102395"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.105962"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41684-018-0150-4"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:02:19Z","timestamp":1761069739000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/path.6382"],"URL":"https:\/\/doi.org\/10.1002\/path.6382","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,13]]},"assertion":[{"value":"2024-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}