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
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Publicado: Nature Portfolio 2020
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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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