S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells

Abstract To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell–cell interactions between the MCF10A cells...

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Autores principales:	Seol Hwa Jo, Woo Hang Heo, Hye-Youn Son, Mingji Quan, Bok Sil Hong, Ju Hee Kim, Han-Byoel Lee, Wonshik Han, Yeonju Park, Dong-Sup Lee, Nam Hoon Kwon, Min Chul Park, Jeesoo Chae, Jong-Il Kim, Dong-Young Noh, Hyeong-Gon Moon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ff6cf20ce724434eac10c56824e1daea
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spelling	oai:doaj.org-article:ff6cf20ce724434eac10c56824e1daea2021-12-02T14:01:21ZS100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells10.1038/s41598-020-80625-22045-2322https://doaj.org/article/ff6cf20ce724434eac10c56824e1daea2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80625-2https://doaj.org/toc/2045-2322Abstract To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell–cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Direct co-culture showed most distinct phenotype changes in MCF10A cells followed by conditioned media treatment and indirect co-culture. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell–cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.Seol Hwa JoWoo Hang HeoHye-Youn SonMingji QuanBok Sil HongJu Hee KimHan-Byoel LeeWonshik HanYeonju ParkDong-Sup LeeNam Hoon KwonMin Chul ParkJeesoo ChaeJong-Il KimDong-Young NohHyeong-Gon MoonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seol Hwa Jo Woo Hang Heo Hye-Youn Son Mingji Quan Bok Sil Hong Ju Hee Kim Han-Byoel Lee Wonshik Han Yeonju Park Dong-Sup Lee Nam Hoon Kwon Min Chul Park Jeesoo Chae Jong-Il Kim Dong-Young Noh Hyeong-Gon Moon S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
description	Abstract To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell–cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Direct co-culture showed most distinct phenotype changes in MCF10A cells followed by conditioned media treatment and indirect co-culture. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell–cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.
format	article
author	Seol Hwa Jo Woo Hang Heo Hye-Youn Son Mingji Quan Bok Sil Hong Ju Hee Kim Han-Byoel Lee Wonshik Han Yeonju Park Dong-Sup Lee Nam Hoon Kwon Min Chul Park Jeesoo Chae Jong-Il Kim Dong-Young Noh Hyeong-Gon Moon
author_facet	Seol Hwa Jo Woo Hang Heo Hye-Youn Son Mingji Quan Bok Sil Hong Ju Hee Kim Han-Byoel Lee Wonshik Han Yeonju Park Dong-Sup Lee Nam Hoon Kwon Min Chul Park Jeesoo Chae Jong-Il Kim Dong-Young Noh Hyeong-Gon Moon
author_sort	Seol Hwa Jo
title	S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
title_short	S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
title_full	S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
title_fullStr	S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
title_full_unstemmed	S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
title_sort	s100a8/a9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ff6cf20ce724434eac10c56824e1daea
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S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell–cell interactions with adjacent breast cancer cells

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