{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:24Z","timestamp":1792789044121,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["FP7\/2007-2013\/grant agreement nr. 316610"],"award-info":[{"award-number":["FP7\/2007-2013\/grant agreement nr. 316610"]}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2016.113.1"],"award-info":[{"award-number":["2016.113.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC1003-CiM"],"award-info":[{"award-number":["EXC1003-CiM"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming growth factor-\u03b2 (TGF-\u03b2), and stromal matrix proteins, such as laminin-332, are factors which promote CAF differentiation. In a spheroid culture system, differentiation of CAFs was analysed for laminin-332 production, laminin-binding integrin repertoire, adhesion and migration behaviour, and, in heterospheroids, for their interplay with the pancreatic duct adenocarcinoma AsPC-I cells. Our data reveal that CAFs produce laminin-332 thus contributing to its ectopic deposition within the tumour stroma. Moreover, CAF differentiation correlates with an increased expression of \u03b13\u03b21 integrin, the principal laminin-332-receptor. Beyond its role as novel CAF marker protein, integrin \u03b13\u03b21 crucially determines differentiation and maintenance of the CAF phenotype, as knock-out of the integrin \u03b13 subunit reversed the CAF differentiated state. AsPC-I cells co-cultured in heterospheroids with integrin \u03b13-deficient CAFs invaded less than from heterospheroids with wild-type CAFs. This study highlights the role of integrin \u03b13\u03b21 integrin-laminin-332 interaction of CAFs which promotes and sustains differentiation of CAFs and promotes carcinoma invasion.<\/jats:p>","DOI":"10.3390\/cancers11010014","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T12:14:49Z","timestamp":1545394489000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The Interaction between Laminin-332 and \u03b13\u03b21 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-1979","authenticated-orcid":false,"given":"Ana C.","family":"Martins Cavaco","sequence":"first","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-9026","authenticated-orcid":false,"given":"Michele F.","family":"Caliandro","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-1226","authenticated-orcid":false,"given":"Augusto","family":"Martins Lima","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stehling","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, R\u00f6ntgenstra\u00dfe 20, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer A.","family":"Dhayat","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1 (W1), 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Haier","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1 (W1), 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cord","family":"Brakebusch","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maal\u00f8es vej 5, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2137","authenticated-orcid":false,"given":"Johannes A.","family":"Eble","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nrc949","article-title":"Pancreatic cancer biology and genetics","volume":"2","author":"Bardeesy","year":"2002","journal-title":"Nat. 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