Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis

Abstract Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithe...

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Autores principales:	Anna Stejskalová, Victoria Fincke, Melissa Nowak, Yvonne Schmidt, Katrin Borrmann, Marie-Kristin von Wahlde, Sebastian D. Schäfer, Ludwig Kiesel, Burkhard Greve, Martin Götte
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8b9f85f6a7e4d00ad06a95a5e0ba396
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spelling	oai:doaj.org-article:b8b9f85f6a7e4d00ad06a95a5e0ba3962021-12-02T14:04:00ZCollagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis10.1038/s41598-021-83645-82045-2322https://doaj.org/article/b8b9f85f6a7e4d00ad06a95a5e0ba3962021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83645-8https://doaj.org/toc/2045-2322Abstract Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithelial endometriotic (12Z) and co-culture (1:1 St-T1b:12Z) spheroids to mimic the architecture of endometrium, and either collagen I or Matrigel to model ectopic locations. Stromal spheroids, but not single cells, assumed coordinated directional migration followed by matrix remodeling of collagen I on day 5 or 7, resembling ectopic lesions. While generally a higher area fold increase of spheroids occurred on collagen I compared to Matrigel, directional migration was not observed in co-culture or in 12Z cells. The fold increase in area on collagen I was significantly reduced by MMP inhibition in stromal but not 12Z cells. Inhibiting ROCK signalling responsible for actomyosin contraction increased the fold increase of area and metabolic activity compared to untreated controls on Matrigel. The number of protrusions emanating from 12Z spheroids on Matrigel was decreased by microRNA miR-200b and increased by miR-145. This study demonstrates that spheroid assay is a promising pre-clinical tool that can be used to evaluate small molecule drugs and microRNA-based therapeutics for endometriosis.Anna StejskalováVictoria FinckeMelissa NowakYvonne SchmidtKatrin BorrmannMarie-Kristin von WahldeSebastian D. SchäferLudwig KieselBurkhard GreveMartin GötteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Stejskalová Victoria Fincke Melissa Nowak Yvonne Schmidt Katrin Borrmann Marie-Kristin von Wahlde Sebastian D. Schäfer Ludwig Kiesel Burkhard Greve Martin Götte Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
description	Abstract Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithelial endometriotic (12Z) and co-culture (1:1 St-T1b:12Z) spheroids to mimic the architecture of endometrium, and either collagen I or Matrigel to model ectopic locations. Stromal spheroids, but not single cells, assumed coordinated directional migration followed by matrix remodeling of collagen I on day 5 or 7, resembling ectopic lesions. While generally a higher area fold increase of spheroids occurred on collagen I compared to Matrigel, directional migration was not observed in co-culture or in 12Z cells. The fold increase in area on collagen I was significantly reduced by MMP inhibition in stromal but not 12Z cells. Inhibiting ROCK signalling responsible for actomyosin contraction increased the fold increase of area and metabolic activity compared to untreated controls on Matrigel. The number of protrusions emanating from 12Z spheroids on Matrigel was decreased by microRNA miR-200b and increased by miR-145. This study demonstrates that spheroid assay is a promising pre-clinical tool that can be used to evaluate small molecule drugs and microRNA-based therapeutics for endometriosis.
format	article
author	Anna Stejskalová Victoria Fincke Melissa Nowak Yvonne Schmidt Katrin Borrmann Marie-Kristin von Wahlde Sebastian D. Schäfer Ludwig Kiesel Burkhard Greve Martin Götte
author_facet	Anna Stejskalová Victoria Fincke Melissa Nowak Yvonne Schmidt Katrin Borrmann Marie-Kristin von Wahlde Sebastian D. Schäfer Ludwig Kiesel Burkhard Greve Martin Götte
author_sort	Anna Stejskalová
title	Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
title_short	Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
title_full	Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
title_fullStr	Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
title_full_unstemmed	Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis
title_sort	collagen i triggers directional migration, invasion and matrix remodeling of stroma cells in a 3d spheroid model of endometriosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b8b9f85f6a7e4d00ad06a95a5e0ba396
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Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis

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