Generation of ductal organoids from normal mammary luminal cells reveals invasive potential
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. Thereby, we find that ductal structures are gene...
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| Veröffentlicht in: | The Journal of pathology 2021-12, Vol.255 (4), p.451-463 |
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| creator | Ganz, Hilary M Buchmann, Benedikt Engelbrecht, Lisa K Jesinghaus, Moritz Eichelberger, Laura Gabka, Christian J Schmidt, Georg P Muckenhuber, Alexander Weichert, Wilko Bausch, Andreas R Scheel, Christina H |
| description | 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. 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, 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 no special type 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. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. |
| doi_str_mv | 10.1002/path.5790 |
| format | Article |
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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, 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 no special type 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. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.5790</identifier><identifier>PMID: 34467523</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Actomyosin ; apical‐basal polarity ; branching morphogenesis ; Breast cancer ; Breast Neoplasms - pathology ; Carcinoma ; Carcinoma, Ductal, Breast - pathology ; Cell Culture Techniques - methods ; Contractility ; ductal ; Epithelial Cells - pathology ; Female ; Humans ; invasive breast cancer ; Invasiveness ; luminal progenitor (LP) cell ; Morphogenesis ; Morphology ; Neoplasm Invasiveness - pathology ; organoid ; Organoids ; Organoids - pathology ; primary human mammary epithelial cells ; Progenitor cells ; Stem cells</subject><ispartof>The Journal of pathology, 2021-12, Vol.255 (4), p.451-463</ispartof><rights>2021 The Authors. published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2021 The Authors. 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The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</description><subject>Actomyosin</subject><subject>apical‐basal polarity</subject><subject>branching morphogenesis</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Cell Culture Techniques - methods</subject><subject>Contractility</subject><subject>ductal</subject><subject>Epithelial Cells - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>invasive breast cancer</subject><subject>Invasiveness</subject><subject>luminal progenitor (LP) cell</subject><subject>Morphogenesis</subject><subject>Morphology</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>organoid</subject><subject>Organoids</subject><subject>Organoids - pathology</subject><subject>primary human mammary epithelial cells</subject><subject>Progenitor cells</subject><subject>Stem cells</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kDFPwzAQhS0EoqUw8AeQJSaGtE5sx_FYVdAiVYKhTAyW69jgKomDnRT13-NQYGM63b1PT-8eANcpmqYIZbNWdu9Tyjg6AeMU8TzhBc9PwThqWYJJykbgIoQdQohzSs_BCBOSM5rhMXhd6kZ72VnXQGdg2atOVtD5N9k4WwZovKth43wdr7Wsa-kPsOpr28Rd6aoK0Ou9lnHaZi-D3WvYuk43nZXVJTgzUdFXP3MCXh7uN4tVsn5aPi7m60ThokAJNcoYwyjHiKRYliRVLEOcMYwyxIiSBpeaMcSUojH_tpDKZKXkUqJcFyXHE3B79G29--h16MTO9T4mDCKjnPGCUJJH6u5IKe9C8NqI1tvhH5EiMdQohhrFUGNkb34c-22tyz_yt7cIzI7Ap6304X8n8TzfrL4tvwCqW33-</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Ganz, Hilary M</creator><creator>Buchmann, Benedikt</creator><creator>Engelbrecht, Lisa K</creator><creator>Jesinghaus, Moritz</creator><creator>Eichelberger, Laura</creator><creator>Gabka, Christian J</creator><creator>Schmidt, Georg P</creator><creator>Muckenhuber, Alexander</creator><creator>Weichert, Wilko</creator><creator>Bausch, Andreas R</creator><creator>Scheel, Christina H</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0002-0018-5661</orcidid><orcidid>https://orcid.org/0000-0003-0424-9818</orcidid></search><sort><creationdate>202112</creationdate><title>Generation of ductal organoids from normal mammary luminal cells reveals invasive potential</title><author>Ganz, Hilary M ; 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| subjects | Actomyosin apical‐basal polarity branching morphogenesis Breast cancer Breast Neoplasms - pathology Carcinoma Carcinoma, Ductal, Breast - pathology Cell Culture Techniques - methods Contractility ductal Epithelial Cells - pathology Female Humans invasive breast cancer Invasiveness luminal progenitor (LP) cell Morphogenesis Morphology Neoplasm Invasiveness - pathology organoid Organoids Organoids - pathology primary human mammary epithelial cells Progenitor cells Stem cells |
| title | Generation of ductal organoids from normal mammary luminal cells reveals invasive potential |
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