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Fibronectin assembly regulates lumen formation in breast acini

Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that self‐assembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial‐to‐mesen...

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Autores principales: Magdaleno, Carina, House, Trenton, Pawar, Jogendra S., Carvalho, Sophia, Rajasekaran, Narendiran, Varadaraj, Archana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016724/
https://www.ncbi.nlm.nih.gov/pubmed/33438770
http://dx.doi.org/10.1002/jcb.29885
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author Magdaleno, Carina
House, Trenton
Pawar, Jogendra S.
Carvalho, Sophia
Rajasekaran, Narendiran
Varadaraj, Archana
author_facet Magdaleno, Carina
House, Trenton
Pawar, Jogendra S.
Carvalho, Sophia
Rajasekaran, Narendiran
Varadaraj, Archana
author_sort Magdaleno, Carina
collection PubMed
description Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that self‐assembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial‐to‐mesenchymal transition. The role of the FN matrix of epithelial cells in driving such processes remains less well understood and is the focus of this study. Hypoxia, defined by low oxygen tension (<5%) is one of the hallmarks of tumor microenvironments impacting fibril reorganization in stromal and epithelial cells. Here, using the MCF10 breast epithelial progression series of cell lines encompassing normal, preinvasive, and invasive states, we show that FN fibril formation decreases during hypoxia, coinciding with a decrease in migratory potential of these cells. Conversely, we find that FN fibril disruption during three‐dimensional acinar growth of normal breast cells resulted in acinar luminal filling. Our data also demonstrates that the luminal filling upon fibril disruption in untransformed MCF10A cells results in a loss of apicobasal polarity, characteristic of pre‐invasive and invasive breast cell lines MCF10AT and MCF10 DCIS.com. Overall this is the first study that relates fibril‐mediated changes in epithelial cells as critical players in lumen clearing of breast acini and maintenance of the untransformed growth characteristic.
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spelling pubmed-80167242021-04-20 Fibronectin assembly regulates lumen formation in breast acini Magdaleno, Carina House, Trenton Pawar, Jogendra S. Carvalho, Sophia Rajasekaran, Narendiran Varadaraj, Archana J Cell Biochem Research Articles Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that self‐assembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial‐to‐mesenchymal transition. The role of the FN matrix of epithelial cells in driving such processes remains less well understood and is the focus of this study. Hypoxia, defined by low oxygen tension (<5%) is one of the hallmarks of tumor microenvironments impacting fibril reorganization in stromal and epithelial cells. Here, using the MCF10 breast epithelial progression series of cell lines encompassing normal, preinvasive, and invasive states, we show that FN fibril formation decreases during hypoxia, coinciding with a decrease in migratory potential of these cells. Conversely, we find that FN fibril disruption during three‐dimensional acinar growth of normal breast cells resulted in acinar luminal filling. Our data also demonstrates that the luminal filling upon fibril disruption in untransformed MCF10A cells results in a loss of apicobasal polarity, characteristic of pre‐invasive and invasive breast cell lines MCF10AT and MCF10 DCIS.com. Overall this is the first study that relates fibril‐mediated changes in epithelial cells as critical players in lumen clearing of breast acini and maintenance of the untransformed growth characteristic. John Wiley and Sons Inc. 2021-01-13 2021-05 /pmc/articles/PMC8016724/ /pubmed/33438770 http://dx.doi.org/10.1002/jcb.29885 Text en © 2021 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Magdaleno, Carina
House, Trenton
Pawar, Jogendra S.
Carvalho, Sophia
Rajasekaran, Narendiran
Varadaraj, Archana
Fibronectin assembly regulates lumen formation in breast acini
title Fibronectin assembly regulates lumen formation in breast acini
title_full Fibronectin assembly regulates lumen formation in breast acini
title_fullStr Fibronectin assembly regulates lumen formation in breast acini
title_full_unstemmed Fibronectin assembly regulates lumen formation in breast acini
title_short Fibronectin assembly regulates lumen formation in breast acini
title_sort fibronectin assembly regulates lumen formation in breast acini
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016724/
https://www.ncbi.nlm.nih.gov/pubmed/33438770
http://dx.doi.org/10.1002/jcb.29885
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