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Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells

Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates a wide range of biological functions such as cell proliferation, cell apoptosis and angiogenesis. Its cellular level is elevated in breast cancer, which, in turn, would promote cancer cell proliferation, survival, growt...

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Detalles Bibliográficos
Autores principales: Wu, Xiyuan, Wabitsch, Martin, Yang, Jian, Sakharkar, Meena Kishore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204952/
https://www.ncbi.nlm.nih.gov/pubmed/37220155
http://dx.doi.org/10.1371/journal.pone.0286111
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author Wu, Xiyuan
Wabitsch, Martin
Yang, Jian
Sakharkar, Meena Kishore
author_facet Wu, Xiyuan
Wabitsch, Martin
Yang, Jian
Sakharkar, Meena Kishore
author_sort Wu, Xiyuan
collection PubMed
description Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates a wide range of biological functions such as cell proliferation, cell apoptosis and angiogenesis. Its cellular level is elevated in breast cancer, which, in turn, would promote cancer cell proliferation, survival, growth and metastasis. However, the cellular concentration of S1P is normally in the low nanomolar range, and our previous studies showed that S1P selectively induced apoptosis of breast cancer cells at high concentrations (high nanomolar to low micromolar). Thus, local administration of high-concentration S1P alone or in combination of chemotherapy agents could be used to treat breast cancer. The breast mainly consists of mammary gland and connective tissue stroma (adipose), which are dynamically interacting each other. Thus, in the current study, we evaluated how normal adipocyte-conditioned cell culture media (AD-CM) and cancer-associated adipocyte-conditioned cell culture media (CAA-CM) would affect high-concentration S1P treatment of triple-negative breast cancer (TNBC) cells. Both AD-CM and CAA-CM may suppress the anti-proliferative effect and reduce nuclear alteration/apoptosis caused by high-concentration S1P. This implicates that adipose tissue is likely to be detrimental to local high-concentration S1P treatment of TNBC. Because the interstitial concentration of S1P is about 10 times higher than its cellular level, we undertook a secretome analysis to understand how S1P would affect the secreted protein profile of differentiated SGBS adipocytes. At 100 nM S1P treatment, we identified 36 upregulated and 21 downregulated secretome genes. Most of these genes are involved in multiple biological processes. Further studies are warranted to identify the most important secretome targets of S1P in adipocytes and illustrate the mechanism on how these target proteins affect S1P treatment of TNBC.
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spelling pubmed-102049522023-05-24 Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells Wu, Xiyuan Wabitsch, Martin Yang, Jian Sakharkar, Meena Kishore PLoS One Research Article Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates a wide range of biological functions such as cell proliferation, cell apoptosis and angiogenesis. Its cellular level is elevated in breast cancer, which, in turn, would promote cancer cell proliferation, survival, growth and metastasis. However, the cellular concentration of S1P is normally in the low nanomolar range, and our previous studies showed that S1P selectively induced apoptosis of breast cancer cells at high concentrations (high nanomolar to low micromolar). Thus, local administration of high-concentration S1P alone or in combination of chemotherapy agents could be used to treat breast cancer. The breast mainly consists of mammary gland and connective tissue stroma (adipose), which are dynamically interacting each other. Thus, in the current study, we evaluated how normal adipocyte-conditioned cell culture media (AD-CM) and cancer-associated adipocyte-conditioned cell culture media (CAA-CM) would affect high-concentration S1P treatment of triple-negative breast cancer (TNBC) cells. Both AD-CM and CAA-CM may suppress the anti-proliferative effect and reduce nuclear alteration/apoptosis caused by high-concentration S1P. This implicates that adipose tissue is likely to be detrimental to local high-concentration S1P treatment of TNBC. Because the interstitial concentration of S1P is about 10 times higher than its cellular level, we undertook a secretome analysis to understand how S1P would affect the secreted protein profile of differentiated SGBS adipocytes. At 100 nM S1P treatment, we identified 36 upregulated and 21 downregulated secretome genes. Most of these genes are involved in multiple biological processes. Further studies are warranted to identify the most important secretome targets of S1P in adipocytes and illustrate the mechanism on how these target proteins affect S1P treatment of TNBC. Public Library of Science 2023-05-23 /pmc/articles/PMC10204952/ /pubmed/37220155 http://dx.doi.org/10.1371/journal.pone.0286111 Text en © 2023 Wu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wu, Xiyuan
Wabitsch, Martin
Yang, Jian
Sakharkar, Meena Kishore
Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title_full Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title_fullStr Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title_full_unstemmed Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title_short Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells
title_sort effects of adipocyte-conditioned cell culture media on s1p treatment of human triple-negative breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204952/
https://www.ncbi.nlm.nih.gov/pubmed/37220155
http://dx.doi.org/10.1371/journal.pone.0286111
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