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Ganz, H.M. ; Buchmann, B.* ; Engelbrecht, L.K.* ; Jesinghaus, M.* ; Eichelberger, L.* ; Gabka, C.J.* ; Schmidt, G.P.* ; Muckenhuber, A.* ; Weichert, W.* ; Bausch, A.R.* ; Scheel, C.

Generation of ductal organoids from normal mammary luminal cells reveals invasive potential.

J. Pathol., DOI: 10.1002/path.5790 (2021)
Postprint DOI PMC
Open Access Gold (Paid Option)
Here, we present an experimental model for human luminal progenitor cells that enables single, primary cells isolated from normal tissue to generate complex branched structures resembling the ductal morphology of low-grade carcinoma of no special type (NST). Thereby, we find that ductal structures are generated through invasive branching morphogenesis via matrix-remodeling and identify reduced actomyosin contractility as a prerequisite for invasion. In addition, we show that knockout of E-cadherin causes a dissolution of duct formation as observed in invasive lobular carcinoma (ILC), a subtype of invasive carcinomas where E-cadherin function is frequently lost. Thus, our model shows that invasive capacity can be elicited from normal luminal cells in specific environments which results in low-grade NST morphology. This assay offers a platform to investigate the dynamics of luminal cell invasion and unravel the impact of genetic and non-genetic aberrations on invasive morphology.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apical-basal Polarity ; Branching Morphogenesis ; Ductal ; Invasive Breast Cancer ; Luminal Progenitor (lp) Cell ; Organoid ; Primary Human Mammary Epithelial Cells; Carcinoma In-situ; E-cadherin Expression; Breast-cancer; Myoepithelial Cells; Epithelial-cells; Genetic Predisposition; Stem-cell; Matrix; Progenitors; Migration
ISSN (print) / ISBN 0022-3417
e-ISSN 1096-9896
Journal Journal of Pathology, The
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Grants German Cancer Aid foundation(Integrate-TN)
German Cancer Aid foundation(Deutsche Krebshilfe)
German Cancer Aid foundation (Max Eder Program)
Khaled group (Department of Pharmacology, University of Cambridge)