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Dysregulation of the transmembrane heparan sulphate proteoglycan Syndecan\u20101 (Sdc\u20101) plays a role in tumour progression of invasive breast cancer (IBC). In DCIS, Sdc\u20101, c\u2010Met and E\u2010cadherin are part of a proangiogenic expression signature. In this study, we employed a siRNA knockdown approach in the DCIS model cell line MCF10A DCIS.com to investigate a potential connection between Sdc\u20101 and epithelial mesenchymal transition (EMT), proteolysis and the Rho kinase pathway. Analysis of gene expression data of the TNMplot.com database revealed that Sdc\u20101 expression was higher in primary breast tumours compared to metastases. The impact of Sdc\u20101\u2010depletion on the cellular phenotype was investigated in a Matrigel\u2010based three\u2010dimensional cell culture model. Sdc\u20101 depletion resulted in the formation of larger spheroids and the formation of invasive protrusions. Application of matrix metalloproteinase (MMP) and Rho kinase inhibitors could block the Sdc\u20101\u2010induced phenotype. qPCR analysis of Sdc\u20101\u2010depleted cells in two\u2010dimensional culture revealed upregulated expression of the EMT\u2010markers CDH1, FN\u20101, CLDN1, the proteolysis markers MMP3, and MMP9, and HPSE, while MMP2, VIM and ROCK\u20102 were downregulated. Immunocytochemistry confirmed upregulation of MMP9 and fibronectin, the latter being particular prominent after ROCK inhibition. STRING analysis confirmed an interaction of the investigated gene products at the protein level. Our results suggest that diminished Sdc\u20101 expression plays a role in DCIS progression to IBC through deregulation of proteolytic factors and a partial EMT.<\/jats:p>","DOI":"10.1002\/iub.2623","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T10:29:24Z","timestamp":1652956164000},"page":"955-968","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The heparan sulphate proteoglycan Syndecan\u20101 (<scp>CD138<\/scp>) regulates tumour progression in a 3D model of ductal carcinoma in situ of the breast"],"prefix":"10.1002","volume":"74","author":[{"given":"Christopher","family":"D'Arcy","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics M\u00fcnster University Hospital  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa 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