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


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2023
Historique:
received: 03 01 2023
accepted: 09 05 2023
medline: 25 5 2023
pubmed: 23 5 2023
entrez: 23 5 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37220155
doi: 10.1371/journal.pone.0286111
pii: PONE-D-23-00212
pmc: PMC10204952
doi:

Substances chimiques

sphingosine 1-phosphate 26993-30-6
Lysophospholipids 0
Culture Media, Conditioned 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0286111

Informations de copyright

Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Xiyuan Wu (X)

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.

Martin Wabitsch (M)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

Jian Yang (J)

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.

Meena Kishore Sakharkar (MK)

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.

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