Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression

Abstract Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast c...

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Autores principales:	Wei Bin Fang, Diana Sofia Acevedo, Curtis Smart, Brandon Zinda, Nadia Alissa, Kyle Warren, Garth Fraga, Li-Ching Huang, Yu Shyr, Wei Li, Lu Xie, Vincent Staggs, Yan Hong, Fariba Behbod, Nikki Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e457ae5a93a494ea906c23486258ba4
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spelling	oai:doaj.org-article:5e457ae5a93a494ea906c23486258ba42021-12-02T17:32:58ZExpression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression10.1038/s41598-021-88229-02045-2322https://doaj.org/article/5e457ae5a93a494ea906c23486258ba42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88229-0https://doaj.org/toc/2045-2322Abstract Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.Wei Bin FangDiana Sofia AcevedoCurtis SmartBrandon ZindaNadia AlissaKyle WarrenGarth FragaLi-Ching HuangYu ShyrWei LiLu XieVincent StaggsYan HongFariba BehbodNikki ChengNature 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 Wei Bin Fang Diana Sofia Acevedo Curtis Smart Brandon Zinda Nadia Alissa Kyle Warren Garth Fraga Li-Ching Huang Yu Shyr Wei Li Lu Xie Vincent Staggs Yan Hong Fariba Behbod Nikki Cheng Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
description	Abstract Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.
format	article
author	Wei Bin Fang Diana Sofia Acevedo Curtis Smart Brandon Zinda Nadia Alissa Kyle Warren Garth Fraga Li-Ching Huang Yu Shyr Wei Li Lu Xie Vincent Staggs Yan Hong Fariba Behbod Nikki Cheng
author_facet	Wei Bin Fang Diana Sofia Acevedo Curtis Smart Brandon Zinda Nadia Alissa Kyle Warren Garth Fraga Li-Ching Huang Yu Shyr Wei Li Lu Xie Vincent Staggs Yan Hong Fariba Behbod Nikki Cheng
author_sort	Wei Bin Fang
title	Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
title_short	Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
title_full	Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
title_fullStr	Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
title_full_unstemmed	Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
title_sort	expression of ccl2/ccr2 signaling proteins in breast carcinoma cells is associated with invasive progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5e457ae5a93a494ea906c23486258ba4
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Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression

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