Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution
Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Mic...
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sg-ntu-dr.10356-873452023-02-28T17:00:55Z Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution Chung, Hwa Hwa Or, Yu Zuan Shrestha, Smeeta Loh, Jia Tong Lim, Chew Leng Ong, Zoe Woo, Amanda Rui En Su, I-hsin Lin, Valerie Chun Ling School of Biological Sciences Estrogen Mammary Involution Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue. More interestingly, neutrophil depletion diminished estrogen-induced growth of ERα-negative mammary tumor 4T1 in Balb/c mice. These findings highlight a novel aspect of estrogen action that reprograms the activity of neutrophils to create a pro-tumoral microenvironment during mammary involution. This effect on the microenvironment would conceivably aggravate its known neoplastic effect on mammary epithelial cells. MOE (Min. of Education, S’pore) Published version 2018-02-09T03:11:21Z 2019-12-06T16:39:58Z 2018-02-09T03:11:21Z 2019-12-06T16:39:58Z 2017 Journal Article Chung, H. H., Or, Y. Z., Shrestha, S., Loh, J. T., Lim, C. L., Ong, Z., et al. (2017). Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution. Scientific Reports, 7, 46485-. 2045-2322 https://hdl.handle.net/10356/87345 http://hdl.handle.net/10220/44423 10.1038/srep46485 en Scientific Reports © 2017 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 13 p. application/pdf |
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Estrogen Mammary Involution Chung, Hwa Hwa Or, Yu Zuan Shrestha, Smeeta Loh, Jia Tong Lim, Chew Leng Ong, Zoe Woo, Amanda Rui En Su, I-hsin Lin, Valerie Chun Ling Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
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Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue. More interestingly, neutrophil depletion diminished estrogen-induced growth of ERα-negative mammary tumor 4T1 in Balb/c mice. These findings highlight a novel aspect of estrogen action that reprograms the activity of neutrophils to create a pro-tumoral microenvironment during mammary involution. This effect on the microenvironment would conceivably aggravate its known neoplastic effect on mammary epithelial cells. |
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School of Biological Sciences |
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School of Biological Sciences Chung, Hwa Hwa Or, Yu Zuan Shrestha, Smeeta Loh, Jia Tong Lim, Chew Leng Ong, Zoe Woo, Amanda Rui En Su, I-hsin Lin, Valerie Chun Ling |
format |
Article |
author |
Chung, Hwa Hwa Or, Yu Zuan Shrestha, Smeeta Loh, Jia Tong Lim, Chew Leng Ong, Zoe Woo, Amanda Rui En Su, I-hsin Lin, Valerie Chun Ling |
author_sort |
Chung, Hwa Hwa |
title |
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
title_short |
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
title_full |
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
title_fullStr |
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
title_full_unstemmed |
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
title_sort |
estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution |
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2018 |
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https://hdl.handle.net/10356/87345 http://hdl.handle.net/10220/44423 |
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1759854073915375616 |