The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems

The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of mater...

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Autores principales: Andreas Svanström, Jennifer Rosendahl, Simona Salerno, Emma Jonasson, Joakim Håkansson, Anders Ståhlberg, Göran Landberg
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/4105481e86ee49969ddf2eda24fb9b7d
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spelling oai:doaj.org-article:4105481e86ee49969ddf2eda24fb9b7d2021-11-11T14:29:09ZThe Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems2296-418510.3389/fbioe.2021.711977https://doaj.org/article/4105481e86ee49969ddf2eda24fb9b7d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.711977/fullhttps://doaj.org/toc/2296-4185The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of material composition and microenvironment. Of particular interest, the response can be different in a normoxic and hypoxic culturing conditions, which in turn may alter the conclusion regarding a successful recreation of the microenvironment. This study aimed at determining the role of such environments to the conclusion of a better resembling cell culture model to native tissue. Here, the breast cancer cell line MCF7 was cultured in normoxic and hypoxic conditions on patient-derived scaffolds and compared at mRNA and protein levels to cells cultured on 3D printed scaffolds, Matrigel, and conventional 2D plastics. Specifically, a wide range of mRNA targets (40), identified as being regulated upon hypoxia and traditional markers for cell traits (cancer stem cells, epithelial–mesenchymal transition, pluripotency, proliferation, and differentiation), were used together with a selection of corresponding protein targets. 3D cultured cells were vastly different to 2D cultured cells in gene expression and protein levels on the majority of the selected targets in both normoxic and hypoxic culturing conditions. By comparing Matrigel and 3DPS-cultured cells to cells cultured on patient-derived scffolds, differences were also noted along all categories of mRNA targets while specifically for the GLUT3 protein. Overall, cells cultured on patient-derived scaffolds closely resembled cells cultured on 3D printed scaffolds, contrasting 2D and Matrigel-cultured cells, regardless of a normoxic or hypoxic culturing condition. Thus, these data support the use of either a normoxic or hypoxic culturing condition in assays using native tissues as a blueprint to optimize material composition.Andreas SvanströmJennifer RosendahlJennifer RosendahlSimona SalernoEmma JonassonJoakim HåkanssonJoakim HåkanssonAnders StåhlbergAnders StåhlbergAnders StåhlbergGöran LandbergGöran LandbergFrontiers Media S.A.article3D printed scaffolds (3DPS)alginatepatient-derived scaffolds (PDS)breast cancernormoxiahypoxiaBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic 3D printed scaffolds (3DPS)
alginate
patient-derived scaffolds (PDS)
breast cancer
normoxia
hypoxia
Biotechnology
TP248.13-248.65
spellingShingle 3D printed scaffolds (3DPS)
alginate
patient-derived scaffolds (PDS)
breast cancer
normoxia
hypoxia
Biotechnology
TP248.13-248.65
Andreas Svanström
Jennifer Rosendahl
Jennifer Rosendahl
Simona Salerno
Emma Jonasson
Joakim Håkansson
Joakim Håkansson
Anders Ståhlberg
Anders Ståhlberg
Anders Ståhlberg
Göran Landberg
Göran Landberg
The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
description The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of material composition and microenvironment. Of particular interest, the response can be different in a normoxic and hypoxic culturing conditions, which in turn may alter the conclusion regarding a successful recreation of the microenvironment. This study aimed at determining the role of such environments to the conclusion of a better resembling cell culture model to native tissue. Here, the breast cancer cell line MCF7 was cultured in normoxic and hypoxic conditions on patient-derived scaffolds and compared at mRNA and protein levels to cells cultured on 3D printed scaffolds, Matrigel, and conventional 2D plastics. Specifically, a wide range of mRNA targets (40), identified as being regulated upon hypoxia and traditional markers for cell traits (cancer stem cells, epithelial–mesenchymal transition, pluripotency, proliferation, and differentiation), were used together with a selection of corresponding protein targets. 3D cultured cells were vastly different to 2D cultured cells in gene expression and protein levels on the majority of the selected targets in both normoxic and hypoxic culturing conditions. By comparing Matrigel and 3DPS-cultured cells to cells cultured on patient-derived scffolds, differences were also noted along all categories of mRNA targets while specifically for the GLUT3 protein. Overall, cells cultured on patient-derived scaffolds closely resembled cells cultured on 3D printed scaffolds, contrasting 2D and Matrigel-cultured cells, regardless of a normoxic or hypoxic culturing condition. Thus, these data support the use of either a normoxic or hypoxic culturing condition in assays using native tissues as a blueprint to optimize material composition.
format article
author Andreas Svanström
Jennifer Rosendahl
Jennifer Rosendahl
Simona Salerno
Emma Jonasson
Joakim Håkansson
Joakim Håkansson
Anders Ståhlberg
Anders Ståhlberg
Anders Ståhlberg
Göran Landberg
Göran Landberg
author_facet Andreas Svanström
Jennifer Rosendahl
Jennifer Rosendahl
Simona Salerno
Emma Jonasson
Joakim Håkansson
Joakim Håkansson
Anders Ståhlberg
Anders Ståhlberg
Anders Ståhlberg
Göran Landberg
Göran Landberg
author_sort Andreas Svanström
title The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
title_short The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
title_full The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
title_fullStr The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
title_full_unstemmed The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
title_sort effect of hypoxic and normoxic culturing conditions in different breast cancer 3d model systems
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/4105481e86ee49969ddf2eda24fb9b7d
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