Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals

Abstract Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low...

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Autores principales:	Melissa M. Ledet, Rebecca M. Harman, Jennifer C. Fan, Emily Schmitt-Matzen, Maria Elena Diaz-Rubio, Sheng Zhang, Gerlinde R. Van de Walle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/677c1f05e43b459ba7e000ece4babf09
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spelling	oai:doaj.org-article:677c1f05e43b459ba7e000ece4babf092021-12-02T15:09:41ZSecreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals10.1038/s41598-020-77639-12045-2322https://doaj.org/article/677c1f05e43b459ba7e000ece4babf092020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77639-1https://doaj.org/toc/2045-2322Abstract Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low mammary cancer incidence. Specifically, these bioactive factors induced triple-negative breast cancer cell (TNBC) death in vitro and reduced tumorigenicity in a xenograft TNBC mouse model in vivo. RNA deep sequencing showed significant downregulation of genes associated with breast cancer progression in secretome-cultured TNBC cells. Further in-depth multi-omics analysis identified sphingomyelins as key secreted factors, and their role was confirmed via inhibition of the sphingomyelin signaling pathway. We speculate that secreted sphingomyelins in the mammary gland of mammals with a naturally low incidence of mammary cancer mediate the elimination of cancer cells. This study contributes to the growing list of protective mechanisms identified in cancer-proof species.Melissa M. LedetRebecca M. HarmanJennifer C. FanEmily Schmitt-MatzenMaria Elena Diaz-RubioSheng ZhangGerlinde R. Van de WalleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Melissa M. Ledet Rebecca M. Harman Jennifer C. Fan Emily Schmitt-Matzen Maria Elena Diaz-Rubio Sheng Zhang Gerlinde R. Van de Walle Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
description	Abstract Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low mammary cancer incidence. Specifically, these bioactive factors induced triple-negative breast cancer cell (TNBC) death in vitro and reduced tumorigenicity in a xenograft TNBC mouse model in vivo. RNA deep sequencing showed significant downregulation of genes associated with breast cancer progression in secretome-cultured TNBC cells. Further in-depth multi-omics analysis identified sphingomyelins as key secreted factors, and their role was confirmed via inhibition of the sphingomyelin signaling pathway. We speculate that secreted sphingomyelins in the mammary gland of mammals with a naturally low incidence of mammary cancer mediate the elimination of cancer cells. This study contributes to the growing list of protective mechanisms identified in cancer-proof species.
format	article
author	Melissa M. Ledet Rebecca M. Harman Jennifer C. Fan Emily Schmitt-Matzen Maria Elena Diaz-Rubio Sheng Zhang Gerlinde R. Van de Walle
author_facet	Melissa M. Ledet Rebecca M. Harman Jennifer C. Fan Emily Schmitt-Matzen Maria Elena Diaz-Rubio Sheng Zhang Gerlinde R. Van de Walle
author_sort	Melissa M. Ledet
title	Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
title_short	Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
title_full	Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
title_fullStr	Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
title_full_unstemmed	Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
title_sort	secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/677c1f05e43b459ba7e000ece4babf09
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Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals

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