Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy

Abstract Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. A...

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Autores principales:	Esmee Koedoot, Liesanne Wolters, Marcel Smid, Peter Stoilov, Gerhard A. Burger, Bram Herpers, Kuan Yan, Leo S. Price, John W. M. Martens, Sylvia E. Le Dévédec, Bob van de Water
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57418be9999441f5885dc1b1785fe4d6
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spelling	oai:doaj.org-article:57418be9999441f5885dc1b1785fe4d62021-12-02T14:23:23ZDifferential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy10.1038/s41598-021-86664-72045-2322https://doaj.org/article/57418be9999441f5885dc1b1785fe4d62021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86664-7https://doaj.org/toc/2045-2322Abstract Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.Esmee KoedootLiesanne WoltersMarcel SmidPeter StoilovGerhard A. BurgerBram HerpersKuan YanLeo S. PriceJohn W. M. MartensSylvia E. Le DévédecBob van de WaterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Esmee Koedoot Liesanne Wolters Marcel Smid Peter Stoilov Gerhard A. Burger Bram Herpers Kuan Yan Leo S. Price John W. M. Martens Sylvia E. Le Dévédec Bob van de Water Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
description	Abstract Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.
format	article
author	Esmee Koedoot Liesanne Wolters Marcel Smid Peter Stoilov Gerhard A. Burger Bram Herpers Kuan Yan Leo S. Price John W. M. Martens Sylvia E. Le Dévédec Bob van de Water
author_facet	Esmee Koedoot Liesanne Wolters Marcel Smid Peter Stoilov Gerhard A. Burger Bram Herpers Kuan Yan Leo S. Price John W. M. Martens Sylvia E. Le Dévédec Bob van de Water
author_sort	Esmee Koedoot
title	Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
title_short	Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
title_full	Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
title_fullStr	Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
title_full_unstemmed	Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
title_sort	differential reprogramming of breast cancer subtypes in 3d cultures and implications for sensitivity to targeted therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/57418be9999441f5885dc1b1785fe4d6
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Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy

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