Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

Abstract Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive norma...

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Autores principales:	Gokhan Bahcecioglu, Xiaoshan Yue, Erin Howe, Ian Guldner, M. Sharon Stack, Harikrishna Nakshatri, Siyuan Zhang, Pinar Zorlutuna
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	aging breast cancer epithelial‐mesenchymal transition extracellular matrix lysyl oxidase Science Q
Acceso en línea:	https://doaj.org/article/5025621fe6d3440e8deb6ccf156bf09f
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spelling	oai:doaj.org-article:5025621fe6d3440e8deb6ccf156bf09f2021-11-17T08:40:31ZAged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype2198-384410.1002/advs.202100128https://doaj.org/article/5025621fe6d3440e8deb6ccf156bf09f2021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202100128https://doaj.org/toc/2198-3844Abstract Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer‐like phenotype, while promoting motility and invasiveness in MDA‐MB‐231 cells. Decellularized breast matrix from aged mice leads to loss of E‐cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer‐related proteins. The aged matrix upregulates cancer‐related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial‐mesenchymal transition‐related genes. Lysyl oxidase knockdown reverts the aged matrix‐induced changes to the young levels; it relocalizes E‐cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer‐like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.Gokhan BahceciogluXiaoshan YueErin HoweIan GuldnerM. Sharon StackHarikrishna NakshatriSiyuan ZhangPinar ZorlutunaWileyarticleagingbreast cancerepithelial‐mesenchymal transitionextracellular matrixlysyl oxidaseScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aging breast cancer epithelial‐mesenchymal transition extracellular matrix lysyl oxidase Science Q
spellingShingle	aging breast cancer epithelial‐mesenchymal transition extracellular matrix lysyl oxidase Science Q Gokhan Bahcecioglu Xiaoshan Yue Erin Howe Ian Guldner M. Sharon Stack Harikrishna Nakshatri Siyuan Zhang Pinar Zorlutuna Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
description	Abstract Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer‐like phenotype, while promoting motility and invasiveness in MDA‐MB‐231 cells. Decellularized breast matrix from aged mice leads to loss of E‐cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer‐related proteins. The aged matrix upregulates cancer‐related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial‐mesenchymal transition‐related genes. Lysyl oxidase knockdown reverts the aged matrix‐induced changes to the young levels; it relocalizes E‐cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer‐like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.
format	article
author	Gokhan Bahcecioglu Xiaoshan Yue Erin Howe Ian Guldner M. Sharon Stack Harikrishna Nakshatri Siyuan Zhang Pinar Zorlutuna
author_facet	Gokhan Bahcecioglu Xiaoshan Yue Erin Howe Ian Guldner M. Sharon Stack Harikrishna Nakshatri Siyuan Zhang Pinar Zorlutuna
author_sort	Gokhan Bahcecioglu
title	Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
title_short	Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
title_full	Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
title_fullStr	Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
title_full_unstemmed	Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype
title_sort	aged breast extracellular matrix drives mammary epithelial cells to an invasive and cancer‐like phenotype
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/5025621fe6d3440e8deb6ccf156bf09f
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_version_	1718425669836210176

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

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