{"entity": "publication", "iuid": "b6f407d33c69455db3922056e7d80dc7", "timestamp": "2026-08-29T04:17:13.171Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b6f407d33c69455db3922056e7d80dc7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b6f407d33c69455db3922056e7d80dc7"}}, "title": "Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ.", "authors": [{"family": "Strell", "given": "Carina", "initials": "C"}, {"family": "Paulsson", "given": "Janna", "initials": "J"}, {"family": "Jin", "given": "Shao-Bo", "initials": "SB"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Roswall", "given": "Pernilla", "initials": "P"}, {"family": "Mutgan", "given": "Ceren", "initials": "C"}, {"family": "Mitsios", "given": "Nicholas", "initials": "N"}, {"family": "Johansson", "given": "Hemming", "initials": "H"}, {"family": "Wickberg", "given": "Sarah Marie", "initials": "SM"}, {"family": "Svedlund", "given": "Jessica", "initials": "J"}, {"family": "Nilsson", "given": "Mats", "initials": "M"}, {"family": "Hall", "given": "Per", "initials": "P"}, {"family": "Mulder", "given": "Jan", "initials": "J"}, {"family": "Radisky", "given": "Derek C", "initials": "DC"}, {"family": "Pietras", "given": "Kristian", "initials": "K"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Lendahl", "given": "Urban", "initials": "U"}, {"family": "W\u00e4rnberg", "given": "Fredrik", "initials": "F"}, {"family": "\u00d6stman", "given": "Arne", "initials": "A"}], "type": "journal article", "published": "2019-09-01", "journal": {"title": "J. Natl. Cancer Inst.", "issn": "1460-2105", "volume": "111", "issue": "9", "pages": "983-995", "issn-l": "0027-8874"}, "abstract": "A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases.\n\nStromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided.\n\nPDGFR\u03b1(low)/PDGFR\u03b2(high) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype.\n\nA PDGFR\u03b1(low)/PDGFR\u03b2(high) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.", "doi": "10.1093/jnci/djy234", "pmid": "30816935", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6748730"}, {"db": "pii", "key": "5366926"}], "notes": [], "created": "2026-08-21T12:10:17.702Z", "modified": "2026-08-21T12:10:17.728Z"}